DNA molecules encoding murine son of sevenless (mSOS) gene and mSOS polypeptides

ABSTRACT

Isolated DNA molecules comprising a nucleotide sequence encoding murine son of sevenless gene 1 (mSOS1) polypeptide and comprising a nucleotide sequence encoding murine son of sevenless gene 2 (mSOS2) polypeptide are disclosed, as well as isolated mSOS1 polypeptide and isolated mSOS2 polypeptide, and diagnostic methods using the same.

This invention broadly relates to polynucleotides encoding mammalian Sosgene and protein product thereof.

Protein tyrosine kinases (PTKs) are important regulatory proteins thatcontrol many aspects of cellular growth, differentiation, and metabolism(Cantley et al., 1991). Many polypeptide hormones are known to regulatethe metabolism, differentiation, and growth of target cells by bindingtransmembrane receptors that possess intracellular PTK domains (Crossand Dexter, 1991).

The biological effects of PTK activation throughout mammalian cells maybe mediated, at least in part, via the Ras proteins (Simon et al., Cell,Vol. 67, 701-716). Ras genes and protein products are associated with avariety of human tumours, particularly where Ras is overproduced orinappropriately expressed.

Simon et al. (Supra) identified a Drosophila gene, associated withprotein tyrosine kinase signalling. The Drosophila son of sevenless(Sos) gene product is homologous to a yeast protein (CDC25), which is anactivator of guanine nucleotide exchange by Ras proteins. The data ofSimon et al. (Supra) indicates that tyrosine kinase signalling iseffected by activation of the Sos protein (such as via tyrosinephosphorylation, or some form of indirect stimulation), which thenactivates Ras proteins by exchange GDP for GTP.

We have surprisingly identified the mammalian Sos gene, hereinafterreferred to as mSos, fragments thereof, which have homology to variousguanine exchange factors.

In accordance with a first aspect of this invention, there is provided apolynucleotide encoding an mSos gene, or a fragment or analogue thereof.This invention includes any mammalian Sos including human, domesticanimal (sheep, cattle, etc) and companion animal (cats, dog, etc) mSos.

The term polynucleotide as referred to herein refers to DNA and RNA, andderivatives thereof as are well known in the art

Partial nucleotide sequences of the murine mSos genes mSos1 (SEQ IDNO:1) and mSos2 (SEQ ID NO:3) are shown in FIGS. 1 and 2. This inventionincludes such polynucleotide sequences and their full lengthequivalents, as well as analogues thereof where one or more nucleotidesare substituted, deleted or inserted. Methods for the generation ofpolynucleotide analogues are well known in the art.

This invention includes vectors, such as plasmid, viral or other vectorsas are well known in the art, which include a polynucleotide encodingmSos or a fragment or analogue thereof.

In another aspect of this invention, there is provided an mSospolypeptide or fragment or analogue thereof. The amino acid sequence oftwo murine mSos polypeptides, referred to as mSos 1 (SEQ ID NO:2) andmSos 2 (SEQ ID NO:4) are shown in FIGS. 1 and 2, compared to thedrosophila Sos protein product. This invention extends to any mammalianmSos polypeptide, fragment or analogue thereof, including human,domestic animal and companion animal mSos polypeptide.

Reference to mSos polynucleotide fragments, or mSos polypeptidefragments, is to be taken to mean fragments which are unique to mSos.Such fragments will generally comprise in excess of twenty nucleotides,or 20 amino acids, and in particular correspond to a central domain ofabout 430 amino acids, which is homologous to a number of yeast guaninenucleotide exchange factors (as depicted in FIGS. 3a and 3b (SEQ IDNOS:1 and 3)).

Analogues of mSos polypeptides include amino acid modifications,deletions, substitutions, derivitizations and insertions of one or moreamino acids.

It is stressed that this invention extends to mammalian Sos (mSos), inparticular human. While this invention is exemplified with reference tomurine Sos, the invention is clearly not so limited. Reference to mSosmeans any mammalian Sos gene or polypeptide, which may be isolated andcharacterised in accordance with this invention. For example, human mSospolynucleotides may be isolated by hybridization of murine mSospolynucleotides or fragments thereof to human cDNA or genomic sequencesfollowed by isolation and characterisation of hybridising species.Mammals may have several forms of mSos, all of which are involved asregulators/effectors of tyrosine kinase signalling. All such forms ofmSos are within the scope of this invention.

Mutations in the natural mammalian Sos genes, and gene products, mayresult in specific genetic defects, or tumour formation, given the roleof mSos in PTK activation via Ras genes and protein products.

Accordingly, this invention extends to a method of detecting mutant mSosgenes in an individual associated with a pathological phenotype (wherepathological phenotype refers to any pathological condition), whichmethod comprises comparing the nucleotide sequence or chromosomallocation or structure of a suspected mutant mSos gene with a referencenon mutated mSos gene as herein described. Suitable comparisons may bemade by nucleotide sequencing, restriction fragment polymorphism,analysis of amplified products (such as by PCR), and other well knowntechniques in the art. Such methods may be used in genetic counselling,prenatal diagnosis or the like.

According to a further aspect of this invention there is provided anantagonist of mSos which comprises a compound having the same or similarthree-dimensional structure as an mSos polypeptide or a fragmentthereof, which blocks the interations between mSos and its substrate inthe PTK signalling pathway. The invention further relates to apolynucleotide capable of blocking transcription or translation of mSosor fragments thereof. The polynucleotide may be in the form of a triplehelix forming polynucleotide, an antisense polynucleotide or a ribozyme,as are well known in the art.

This invention will now be described by way of example only, withreference to the following non-limiting Figures and Examples. In theFigures:

FIG. 1: shows the nucleotide sequence (SEQ ID NO:1) and predicted aminoacid sequence (SEQ ID NO:2) of the mSos 1 gene;

FIG. 2: shows the nucleotide sequence (SEQ ID NO:3) and predicted aminoacid sequence (SEQ ID NO:4) of the mSos 2 gene;

FIG. 3: shows the partial nucleotide sequence of mSos 1 and mSos 2wherein the nucleotide sequences are aligned to maximise homology;

FIG. 4a: Predicted amino acid sequence of the mSos1 (SEQ ID NO:6) andmSos2 (SEQ ID NO:4) genes and their aligned with Drosophila Sos4(SEQ IDNO:5). Identical residues are in black boxes, conservative substitutionsin grey boxes.

FIG. 4b: Alternate aminoterminal coding regions of the mSos1 gene (SEQID NOS:7 and 8) identified by 5' RACE (Frohman, M. A. and Martin, G. R.,1988). The sequence of the mSos1 gene was derived from a composite ofcDNA clones and 5' RACE products. The majority of RACE products (type 2)(SEQ ID NO:8) terminated before reaching a potential initiatingmethionine in a highly GC region that could not be processed by reversetranscriptase. An alternate RACE product was identified (type 1) (SEQ IDNO:7) which diverged from this sequence as indicated and extended to apotential methionine initiation codon and upstream stop codon. Themolecular weight of the predicted protein is 150 kd;

FIG. 5a: Alignment of the predicted Drosophila (SEQ ID NO:9) and mouseSos proteins (SEQ ID NOS:10 and 11) with four related yeast proteinscdc25 (SEQ ID NO:12), sdc25 (SEQ ID NO:13), ste6 (SEQ ID NO:14) and buds(SEQ ID NO:15).

FIG. 5b: Schematic representation showing the size of each protein andthe relative position of the conserved domain shown in (a) within eachprotein. Percentages indicate the degree of amino acid identity betweena given domain and cdc25; and

FIG. 6: Northern blot analysis of RNA derived from a range of (a) mouseembryonic and adult tissues and (b) continuous mouse and human celllines. Transcripts of 5.4 kb and 8.4 kb were detected with an mSos1probe in all tissues and cell lines tested. Variation in signalintensity was mainly due to differences in the amount and quality of RNA(see control CAODH probe). Additional smaller transcripts were apparentin testes RNA. A single major transcript of 5.6 kb was detected with anmSos2 probe, expressed at apparently comparable levels of mSos1. Adulttissues are indicated. Embryonic tissues were from heads and bodies ofembryos whose stage of gestation was estimated from the time of pluggingof the donor females. Mouse cell lines are, 3T3, Balb/c fibroblast; FN4,erythroid; FDCP1, myeloid; J774, macrophage; ABLS8, preB lymphoid, W279,B lymphoid, MPC11, plasmacytoma; EL4, early T lymphoid and W7.1, Tlymphoid. Transcripts of the same size were also detected in RNA fromthe human erythroleukaemic cell line K562. GAPDH was used as a controlprobe for the amount and quality of RNA.

EXAMPLE 1

A fragment of the Drosophila Sos gene (corresponding to amino acids841-1303, Simon et al., Supra) was used to screen mouse embryonic eyeand adult brain cDNA libraries at low stringency.

cDNA clones were isolated from random bred Swiss E17 embryonic eye andBalb/c adult brain (Stratagene) cDNA libraries using a random Sos cDNAfragment. Duplicate nitrocellulose filters were hybridized in 5×SSC,5×Denharts, 5 mM EDTA, 100 μg/ml herring testes DNA, 0.1% SDS at 65° C.for 18 hr and washed in 2×SSC, 0.1% SDS at 50° C. Partial DNA sequenceobtained from two clones confirmed the isolation of two Sos relatedgenes termed mSos1 and mSos2. Subsequent screening of the eye and brainlibraries with these cDNA inserts identified the remainder of theclones, present at approximately 1;150,000 (eye) and 1;250,000 (brain)recombinants. S5' RACE of mSos1 was performed using RNA derived from anadult mouse brain as described previously (Frohman and Martin, 1988) andalso with the modifications of using thermostable reverse transcriptaseTet-Z, Amersham) and prior denaturation of RNA with methyl mercury(Sambrook et al, 1989). Double stranded dideoxy chain termination DNAsequencing was performed on either nested deletions of cDNA cloned inBluescript KS or with specific oligonucleotide primers using standardmethods (Sambrook et al., Supra). The sequence of both strands wasobtained and nucleotide sequence of mSos 1 and 2 is shown in FIGS. 1 and2, (SEQ ID NOS:1 and 3, respectively).

FIG. 3 shows alignment of sequences of partial sequences of mSos 1 andmSos 2 to maximise homology. The nucleotide numbering of FIG. 3 differsfrom FIGS. 1 and 2, as in FIGS. 1 and 2 the protein sequence starts atposition 18, that is, the second methionine residue.

FIG. 4 shows the amino acid sequence of Drosophila (Sos) and mouse Sos(mSos) proteins. The sequence is presented using the standard one letteramino acid code The molecular weight of the predicted protein is about150 kd The correct amino acid sequence numbering is shown in FIGS. 1 and2 with the second methinone residue in mSos representing the start oftranslation.

The predicted amino acid sequence for mSos2 (SEQ ID NO:4) extended towithin 85 amino acids of the aminoterminal end of Sos (FIG. 4a). Sosshows an overall amino acid identity to both mSos1 and mSos2 of 45%.Both mSos1 and mSos2 remain colinear with SoS over their coding regions,with the exception of their carboxyterminal ends where homology betweenSos and the murine genes is more scattered. Comparison of the two murinegenes shows that they share approximately 67 amino acid identity, withthe lowest degree of similarity residing in the final 270 amino acids(41% identity, FIG. 4a). No significant areas of homology wereidentified when the untranslated regions of the two genes were compared.

FIG. 5 shows alignment of the predicted Drosophila and mouse Sosproteins with four related yeast proteins cdc25, sdc25, ste6 and bud5.

The most notable feature of the Sos and mSos genes is a central domainof approximately 430 amino acids which shows a high degree of homologyto several yeast guanine nucleotide exchange factors, including cdc25,sdc25 and ste6. This domain is present in a fragment of the sdc25 genewhich is capable of catalysing nucleotide exchange by either the yeastRAS2 protein or human c-ras (Crechet at al., 1990), suggesting that theregion of homology between the yeast, Drosophila and mouse genes definesa domain that catalyses nucleotide exchange on ras proteins. Inclusionof the mSos1 and mSos2 in this alignment further highlights residueswhich are highly conserved between the members of this gene family (FIG.3a). Similarity between Sos and Sos and the yeast genes is limited tothis domain.

We have also identified a second domain on both the mSos 1 (amino adds200 to 500 of FIG. 1) and mSos 2 predicted polypeptides which hashomology with the dbl protein, which is a guanine exchange factor for aras-related protein. This suggests that mSos proteins may have separateguanine exchange domains of ras and for ras related proteins.

EXAMPLE 2

RNA isolated from various murine development stages, adult tissues,haemopoietic cell lines, and a human cell line was analysed for Sostranscripts.

Polyadenylated RNA was isolated from tissues and cell lines bydisruption in proteinase K and SDS (Gonda, 1985) and oligo-(dT) affinitychromatography. Two micrograms of RNA from each source was subjected toformaldehyde agarose gel electrophoresis (Sambrook et al, Supra),transferred overnight to Hybond C-super (Amersham) in 20×SSC and thenbaked for 2 hrs. Filters were prehybridized from 4-6 h in 50% formamide,5×SSC, 5×Denhardts, 5 mM EDTA, 100 μg ml-1 herring tests DNA and 0.5%SDS at 42° C. and then hybridized for 18 h. The 32P labelled probes werefrom nt299 to 4464 of mSos1 and from nt1 to 3801 of the available mSos2sequence. Identical results were obtained with non-overlapping probesfrom the 3' untranslated region of each gene (data not shown). Washeswere performed in 0.2×SSC, 0.3% SDS at 65° C. and the filterautoradiographed for 3 days at -70° C. in the presence of anintensifying screen.

As shown in FIG. 6, the mSos1 gene encodes two distinct transcripts of5.4 kb and 8.4 kb that are present in approximately equal abundance.Additional smaller transcripts of 4.8 kb and 3.9 kb were detected in RNAderived from testes (FIG. 6a). The mSos2 gene appears to encode a singletranscript of 5.6 kb. As a cDNA of 5.3 kb has been obtained for mSos2this suggests that the majority of the coding region has been obtainedfor this gene. To investigate whether there was any lineage restrictionin expression of either gene within a given tissue, we tested RNAexpression in haemopoietic cell lines that were representative of earlyand late lymphoid, myeloid and erythroid lineages. Expression of bothmSos1 and mSos2 was detected in all haemopoietic lineages tested and wascomparable to that in Balb/c 3T3 fibroblats (FIG. 6b). The broad patternof expression obtained with mSos1 and mSos2 is consistent with apostulated role in regulating the widely expressed ras proteins.

Northern and Southern blot analysis was also performed using human RNAand DNA. Transcripts corresponding in size to those from mSos1 and mSos2were present in RNA from the human erythroleukaemic cell line K562(Lozzio and Lozzio, 1975) (FIG. 6b) and mSos1 and mSos2 hybridized withhuman genomic DNA when probed at high stringency (data not shown),indicating the presence of separate human genes closely related to bothmSos1 and mSos2, which may be regarded as the human mSos genes.

This invention has been described by way of Example only, and includesall modifications, variations, nucleotide sequences andfragments/analogues thereof, and protein sequences and fragments andanalogues thereof as herein described. Human Sos genes and polypeptides,as well as fragments and analogues thereof, may be isolated andcharacterised according to these Examples.

REFERENCES

Cantley, L. C., et al. (1991) Cell 64, 281-302.

Crechet, J., et al. (1990) Science 248, 866-868.

Cross, M., and Dexter, T. M. (1991) Cell 64, 271-280.

Frohman, M. A., and Martin, G. R (1988) Proc. Natl. Acad. Sci. 85,8998-9002.

Gonda, T. J., et al. (1985) Embo J. 4, 2003-2008.

Lozzio, C. B., and Lozzio, B. B. (1975) Blood 45, 321-334.

Sambrook, J. et al. (1989) Molecular Cloning, Cold Spring HarborLaboratory, New York.

    __________________________________________________________________________    SEQUENCE LISTING                                                              (1) GENERAL INFORMATION:                                                      (iii) NUMBER OF SEQUENCES: 15                                                 (2) INFORMATION FOR SEQ ID NO:1:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 4716 base pairs                                                   (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: DNA (genomic)                                             (ix) FEATURE:                                                                 (A) NAME/KEY: CDS                                                             (B) LOCATION: 22..3975                                                        (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:                                       AAGCAGCACCCCGCGGGCACCATGCAGGCGCAGCAGCTGCCTTACGAGTTT51                         MetGlnAlaGlnGlnLeuProTyrGluPhe                                                1510                                                                          TTCAGCGAGGAGAACGCGCCCAAGTGGCGGGGGCTGCTGGTGCCTGCG99                            PheSerGluGluAsnAlaProLysTrpArgGlyLeuLeuValProAla                              152025                                                                        CTGAAAAAGGTTCAGGGGCAAGTTCACCCTACTCTTGAGTCTAATGAT147                           LeuLysLysValGlnGlyGlnValHisProThrLeuGluSerAsnAsp                              303540                                                                        GATGCTCTTCAGTATGTTGAAGAATTAATTTTGCAATTACTAAATATG195                           AspAlaLeuGlnTyrValGluGluLeuIleLeuGlnLeuLeuAsnMet                              455055                                                                        CTATGCCAAGCTCAGCCCCGGAGTGCTTCAGATGTGGAGGAACGTGTT243                           LeuCysGlnAlaGlnProArgSerAlaSerAspValGluGluArgVal                              606570                                                                        CAAAAGAGTTTTCCTCATCCAATTGATAAGTGGGCAATAGCTGATGCC291                           GlnLysSerPheProHisProIleAspLysTrpAlaIleAlaAspAla                              75808590                                                                      CAATCAGCCATTGAAAAGAGGAAGAGACGAAATCCTTTATCGCTGCCA339                           GlnSerAlaIleGluLysArgLysArgArgAsnProLeuSerLeuPro                              95100105                                                                      GCAGAAAGAATTCATCATTTATTAAGGGAGGTCCTCGGTTATAAAATT387                           AlaGluArgIleHisHisLeuLeuArgGluValLeuGlyTyrLysIle                              110115120                                                                     GACCACCAGGTTTCTGTTTACATAGTAGCAGTATTAGAATACATTTCT435                           AspHisGlnValSerValTyrIleValAlaValLeuGluTyrIleSer                              125130135                                                                     GCAGATATTTTAAAGCTCGTGGGGAATTATGTAAGAAATATACGGCAT483                           AlaAspIleLeuLysLeuValGlyAsnTyrValArgAsnIleArgHis                              140145150                                                                     TATGAAATTACAAAACAAGACATTAAAGTGGCAATGTGTGCTGATAAG531                           TyrGluIleThrLysGlnAspIleLysValAlaMetCysAlaAspLys                              155160165170                                                                  GTATTGATGGATATGTTTCATCAAGATGTAGAAGATATAAATATCTTA579                           ValLeuMetAspMetPheHisGlnAspValGluAspIleAsnIleLeu                              175180185                                                                     TCTTTAACTGATGAAGAGCCTTCCACCTCAGGAGAACAAACTTATTAT627                           SerLeuThrAspGluGluProSerThrSerGlyGluGlnThrTyrTyr                              190195200                                                                     GATTTGGTAAAAGCATTCATGGCAGAAATTCGACAGTATATAAGAGAA675                           AspLeuValLysAlaPheMetAlaGluIleArgGlnTyrIleArgGlu                              205210215                                                                     TTAAATCTAATTATAAAAGTTTTTCGAGAGCCCTTTGTCTCTAATTCC723                           LeuAsnLeuIleIleLysValPheArgGluProPheValSerAsnSer                              220225230                                                                     AAATTGTTTTCATCTAATGATGTAGAAAACATATTCAGTCGTATAGTA771                           LysLeuPheSerSerAsnAspValGluAsnIlePheSerArgIleVal                              235240245250                                                                  GATATACATGAACTTAGTGTAAAGTTACTGGGCCATATAGAAGATACT819                           AspIleHisGluLeuSerValLysLeuLeuGlyHisIleGluAspThr                              255260265                                                                     GTAGAAATGACAGATGAAGGCAGTCCCCACCCATTAGTAGGAAGCTGT867                           ValGluMetThrAspGluGlySerProHisProLeuValGlySerCys                              270275280                                                                     TTTGAAGACTTAGCAGAAGAACTGGCATTTGACCCGTATGAGTCATAT915                           PheGluAspLeuAlaGluGluLeuAlaPheAspProTyrGluSerTyr                              285290295                                                                     GCTCGGGATATTTTACGACCCGGATTCCATGGCCATTTTCTTAGTCAG963                           AlaArgAspIleLeuArgProGlyPheHisGlyHisPheLeuSerGln                              300305310                                                                     TTATCAAAGCCTGGGGCAGCACTTTATTTGCAGTCCATAGGCGAAGGC1011                          LeuSerLysProGlyAlaAlaLeuTyrLeuGlnSerIleGlyGluGly                              315320325330                                                                  TTCAAAGAAGCTGTCCAGTACGTCCTGCCCCGGCTGCTGCTTGCCCCT1059                          PheLysGluAlaValGlnTyrValLeuProArgLeuLeuLeuAlaPro                              335340345                                                                     GTGTACCACTGTCTGCATTACTTTGAACTTCTGAAGCAGTTAGAAGAA1107                          ValTyrHisCysLeuHisTyrPheGluLeuLeuLysGlnLeuGluGlu                              350355360                                                                     AAGAGTGAAGATCAAGAAGACAAGGAGTGTATGAAGCAAGCAATAACA1155                          LysSerGluAspGlnGluAspLysGluCysMetLysGlnAlaIleThr                              365370375                                                                     GCCCTGCTTAATGTCCAAAGTGGCATGGAAAAAATTTGCTCCAAAAGT1203                          AlaLeuLeuAsnValGlnSerGlyMetGluLysIleCysSerLysSer                              380385390                                                                     CTTGCAAAACGAAGACTAAGTGAGTCTGCATGTCGGTTTTACAGCCAG1251                          LeuAlaLysArgArgLeuSerGluSerAlaCysArgPheTyrSerGln                              395400405410                                                                  CAGATGAAGGGGAAACAGCTAGCCATCAAGAAGATGAACGAGATCCAG1299                          GlnMetLysGlyLysGlnLeuAlaIleLysLysMetAsnGluIleGln                              415420425                                                                     AAGAACATTGATGGCTGGGAGGGGAAGGACATTGGACAGTGTTGCAAT1347                          LysAsnIleAspGlyTrpGluGlyLysAspIleGlyGlnCysCysAsn                              430435440                                                                     GAGTTCATAATGGAAGGAACTCTTACACGTGTAGGAGCCAAACACGAG1395                          GluPheIleMetGluGlyThrLeuThrArgValGlyAlaLysHisGlu                              445450455                                                                     AGACACATATTTCTCTTCGATGGCTTAATGATTTGCTGTAAATCAAAC1443                          ArgHisIlePheLeuPheAspGlyLeuMetIleCysCysLysSerAsn                              460465470                                                                     CATGGGCAGCCAAGACTCCCTGGTGCTAGCAGTGCAGAATACCGGCTT1491                          HisGlyGlnProArgLeuProGlyAlaSerSerAlaGluTyrArgLeu                              475480485490                                                                  AAAGAAAAGTTTTTTATGCGAAAGGTACAGATTAATGATAAAGATGAC1539                          LysGluLysPhePheMetArgLysValGlnIleAsnAspLysAspAsp                              495500505                                                                     ACCAGTGAGTACAAGCATGCTTTTGAAATCATTCTGAAAGATGGCAAT1587                          ThrSerGluTyrLysHisAlaPheGluIleIleLeuLysAspGlyAsn                              510515520                                                                     AGTGTTATATTTTCTGCCAAGTCAGCTGAAGAGAAAAACAACTGGATG1635                          SerValIlePheSerAlaLysSerAlaGluGluLysAsnAsnTrpMet                              525530535                                                                     GCAGCACTGATCTCTTTGCAGTACCGCAGCACCCTGGAGAGGATGCTG1683                          AlaAlaLeuIleSerLeuGlnTyrArgSerThrLeuGluArgMetLeu                              540545550                                                                     GACGTAACGGTGCTGCAGGAGGAGAAGGAGGAGCAGATGAGGCTGCCC1731                          AspValThrValLeuGlnGluGluLysGluGluGlnMetArgLeuPro                              555560565570                                                                  AGTGCTGAAGTGTACAGGTTTGCAGAACCTGACTCCGAGGAGAATATT1779                          SerAlaGluValTyrArgPheAlaGluProAspSerGluGluAsnIle                              575580585                                                                     CTATTCGAAGAGAATGTGCAGCCCAAAGCTGGGATCCCCATTATCAAG1827                          LeuPheGluGluAsnValGlnProLysAlaGlyIleProIleIleLys                              590595600                                                                     GCAGGGACAGTGCTTAAGCTCATTGAGAGGCTTACCTACCACATGTAC1875                          AlaGlyThrValLeuLysLeuIleGluArgLeuThrTyrHisMetTyr                              605610615                                                                     GCAGATCCAAATTTTGTTCGGACGTTTCTTACAACATACAGGTCCTTT1923                          AlaAspProAsnPheValArgThrPheLeuThrThrTyrArgSerPhe                              620625630                                                                     TGCAGACCTCAAGAACTACTGAGTCTTCTGATAGAAAGATTTGAAATT1971                          CysArgProGlnGluLeuLeuSerLeuLeuIleGluArgPheGluIle                              635640645650                                                                  CCAGAGCCTGAGCCAACAGAAGCTGATCGCATAGCTATAGAGAATGGA2019                          ProGluProGluProThrGluAlaAspArgIleAlaIleGluAsnGly                              655660665                                                                     GATCAGCCCCTGAGTGCAGAGCTGAAGAGGTTTAGAAAGGAATATATT2067                          AspGlnProLeuSerAlaGluLeuLysArgPheArgLysGluTyrIle                              670675680                                                                     CAGCCTGTGCAGTTGAGGGTGTTAAATGTGTGTCGGCACTGGGTGGAG2115                          GlnProValGlnLeuArgValLeuAsnValCysArgHisTrpValGlu                              685690695                                                                     CACCATTTCTATGACTTTGAAAGAGATGCAGACCTTTTACAGAGAATG2163                          HisHisPheTyrAspPheGluArgAspAlaAspLeuLeuGlnArgMet                              700705710                                                                     GAGGAATTTATTGGAACAGTAAGAGGTAAAGCAATGAAAAAATGGGTC2211                          GluGluPheIleGlyThrValArgGlyLysAlaMetLysLysTrpVal                              715720725730                                                                  GAATCCATCACTAAGATAATCCAAAGGAAAAAAATTGCAAGAGACAAT2259                          GluSerIleThrLysIleIleGlnArgLysLysIleAlaArgAspAsn                              735740745                                                                     GGCCCAGGTCATAACATTACATTTCAGAGCTCACCTCCCACAGTTGAG2307                          GlyProGlyHisAsnIleThrPheGlnSerSerProProThrValGlu                              750755760                                                                     TGGCACATAAGCAGACCTGGGCACATAGAGACTTTTGACTTGCTCACC2355                          TrpHisIleSerArgProGlyHisIleGluThrPheAspLeuLeuThr                              765770775                                                                     TTACACCCAATAGAAATTGCTCGGCAACTCACTTTACTTGAATCAGAT2403                          LeuHisProIleGluIleAlaArgGlnLeuThrLeuLeuGluSerAsp                              780785790                                                                     CTATACCGGGCTGTGCAGCCATCAGAATTAGTTGGAAGTGTGTGGACA2451                          LeuTyrArgAlaValGlnProSerGluLeuValGlySerValTrpThr                              795800805810                                                                  AAAGAAGATAAAGAAATTAATTCTCCCAACCTTCTGAAGATGATTCGG2499                          LysGluAspLysGluIleAsnSerProAsnLeuLeuLysMetIleArg                              815820825                                                                     CACACCACTAACCTCACTTTGTGGTTTGAGAAATGTATTGTAGAAACA2547                          HisThrThrAsnLeuThrLeuTrpPheGluLysCysIleValGluThr                              830835840                                                                     GAAAACTTAGAAGAAAGAGTAGCTGTAGTAAGTCGGATAATTGAGATT2595                          GluAsnLeuGluGluArgValAlaValValSerArgIleIleGluIle                              845850855                                                                     CTACAAGTCTTTCAAGAGCTGAACAACTTCAATGGTGTCCTGGAAGTT2643                          LeuGlnValPheGlnGluLeuAsnAsnPheAsnGlyValLeuGluVal                              860865870                                                                     GTCAGTGCTATGAACTCGTCACCTGTTTACAGACTAGACCACACATTT2691                          ValSerAlaMetAsnSerSerProValTyrArgLeuAspHisThrPhe                              875880885890                                                                  GAGCAAATACCAAGCAGACAAAAGAAAATTTTAGAAGAAGCTCATGAA2739                          GluGlnIleProSerArgGlnLysLysIleLeuGluGluAlaHisGlu                              895900905                                                                     TTGAGTGAAGATCACTATAAGAAATATTTGGCAAAACTCAGGTCTATT2787                          LeuSerGluAspHisTyrLysLysTyrLeuAlaLysLeuArgSerIle                              910915920                                                                     AATCCACCGTGTGTGCCTTTCTTTGGAATTTATCTCACAAATATCCTG2835                          AsnProProCysValProPhePheGlyIleTyrLeuThrAsnIleLeu                              925930935                                                                     AAGACAGAAGAGGGCAACCCTGAGGTCCTGAGGAGACACGGGAAAGAG2883                          LysThrGluGluGlyAsnProGluValLeuArgArgHisGlyLysGlu                              940945950                                                                     CTTATTAACTTCAGCAAGAGGAGGAGAGTGGCCGAGATCACAGGCGAG2931                          LeuIleAsnPheSerLysArgArgArgValAlaGluIleThrGlyGlu                              955960965970                                                                  ATCCAGCAGTACCAGAACCAGCCCTACTGCTTACGGGTGGAGCCGGAC2979                          IleGlnGlnTyrGlnAsnGlnProTyrCysLeuArgValGluProAsp                              975980985                                                                     ATCAAGAGGTTCTTTGAAAACTTGAATCCAATGGGAAACAGCATGGAG3027                          IleLysArgPhePheGluAsnLeuAsnProMetGlyAsnSerMetGlu                              9909951000                                                                    AAAGAATTTACAGACTATCTGTTCAACAAATCCCTAGAAATAGAACCC3075                          LysGluPheThrAspTyrLeuPheAsnLysSerLeuGluIleGluPro                              100510101015                                                                  CGGCACCCTAAGCCTCTTCCGAGATTCCCAAAAAAATACAGCTATCCC3123                          ArgHisProLysProLeuProArgPheProLysLysTyrSerTyrPro                              102010251030                                                                  CTAAAATCTCCTGGTGTTCGTCCATCAAATCCAAGACCAGGAACCATG3171                          LeuLysSerProGlyValArgProSerAsnProArgProGlyThrMet                              1035104010451050                                                              AGACATCCCACACCTCTGCAGCAGGAGCCAAGAAAAATTAGCTACAGT3219                          ArgHisProThrProLeuGlnGlnGluProArgLysIleSerTyrSer                              105510601065                                                                  CGGATTCCTGAAAGTGAGACGGAAAGCACAGCATCTGCACCAAACTCC3267                          ArgIleProGluSerGluThrGluSerThrAlaSerAlaProAsnSer                              107010751080                                                                  CCTCGGACCCCACTGACGCCGCCCCCTGCATCTGGCACCTCCAGCAAC3315                          ProArgThrProLeuThrProProProAlaSerGlyThrSerSerAsn                              108510901095                                                                  ACAGATGTTTGCAGCGTGTTCGATTCTGACCACTCGGCAAGCCCTTTT3363                          ThrAspValCysSerValPheAspSerAspHisSerAlaSerProPhe                              110011051110                                                                  CATTCAAGATCTGCTTCAGTCTCATCTATAAGTTTATCCAAGGGCACT3411                          HisSerArgSerAlaSerValSerSerIleSerLeuSerLysGlyThr                              1115112011251130                                                              GATGAAGTGCCTGTCCCCCCTCCTGTACCCCCTCGAAGACGTCCAGAG3459                          AspGluValProValProProProValProProArgArgArgProGlu                              113511401145                                                                  TCTGCCCCAGCTGAATCCTCCCCATCCAAGATTATGTCTAAGCACTTG3507                          SerAlaProAlaGluSerSerProSerLysIleMetSerLysHisLeu                              115011551160                                                                  GACAGCCCCCCAGCTATTCCTCCTAGGCAACCCACATCCAAAGCCTAT3555                          AspSerProProAlaIleProProArgGlnProThrSerLysAlaTyr                              116511701175                                                                  TCACCACGCTATTCAATATCAGATCGGACCTCTATATCAGATCCTCCT3603                          SerProArgTyrSerIleSerAspArgThrSerIleSerAspProPro                              118011851190                                                                  GAAAGCCCTCCCTTGTTACCACCACGGGAACCTGTGAGGACACCTGAT3651                          GluSerProProLeuLeuProProArgGluProValArgThrProAsp                              1195120012051210                                                              GTTTTCTCAAGCTCACCATTACATCTCCAACCTCCTCCTTTGGGCAAA3699                          ValPheSerSerSerProLeuHisLeuGlnProProProLeuGlyLys                              121512201225                                                                  AAGAGTGATCATGGCAACGCCTTCTTCCCAAACAGCCCATCCCCTTTT3747                          LysSerAspHisGlyAsnAlaPhePheProAsnSerProSerProPhe                              123012351240                                                                  ACACCGCCACCCCCCCAAACCCCCTCTCCTCATGGCACGAGAAGGCAT3795                          ThrProProProProGlnThrProSerProHisGlyThrArgArgHis                              124512501255                                                                  CTGCCATCACCACCACTGACACAGGAGATGGACCTCCATTCCATTGCT3843                          LeuProSerProProLeuThrGlnGluMetAspLeuHisSerIleAla                              126012651270                                                                  GGGCCTCCTGTTCCTCCACGACAAAGCACTTCTCAACTTATCCCCAAA3891                          GlyProProValProProArgGlnSerThrSerGlnLeuIleProLys                              1275128012851290                                                              CTCCCTCCAAAAACTTACAAAAGGGAGCACACACACCCATCCATGCAT3939                          LeuProProLysThrTyrLysArgGluHisThrHisProSerMetHis                              129513001305                                                                  AGAGATGGACCACCACTGCTGGAGAATGCCCATTCTTCCTGAGTTCCT3987                          ArgAspGlyProProLeuLeuGluAsnAlaHisSerSer                                       13101315                                                                      CTAAGCTGGGATAGTTTCCTAGCCCCCAGATCCATTGCTGGCAATGGA4035                          TGCACTGAACATGCCAGCACTGGGGAGTTCAAATGAGAACTCCAAACACTAAC4088                     GACTCTACTTCACGATGTAGTATAAGACAATGAGTTTTAACCTACATGGAATTATGGAAT4148              AAAATGGTATTCCAGCTTAGAATGTGGAAACTGATTGCACCTGGAAATCACGTGAAGGGA4208              CTTTTCTGGCCATTGGGCAGAGTCCTCATATTGTGAAGTGATCTTTATCATTAAAGGGAT4268              GGAAAACAGTCTAATGTCCAACAAGCCCATATGTTGACAGTTTTTGTAATTCAAAATATT4328              ATGCACTTTTAAAAAATCTTAAACAGGGATCTCCTCCTTTGTTTTCCTTTGCTTTACTCT4388              TCTACTTTAGAATATTTTCGTAAAAGTTATTCAGAGGACTGTGAGAAAAGGCTGTGGTAC4448              CTGACCTTGTTGAAATCAAGGCCCAGCACTGTACTACAGTCCTGTTTACAGATTATTACA4508              GTGATCTGAATGGGTACCGAGGCTTCACCAAAAGAGGTACTTTTTGTTATTGTTATTGTT4568              TAAGAATAATTATGCCAATTTAAGAACATCCCCTACCCACCCCCACTCACAAACAAAATG4628              TGGTGGTGTTGCCTTTAAACAAAAAATGTCAATGTCATTAACATGATGGAAGAAGAACAT4688              TTTAAAACGTAACTGTCAAGTATCATTT4716                                              (2) INFORMATION FOR SEQ ID NO:2:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 1319 amino acids                                                  (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: protein                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:                                       MetGlnAlaGlnGlnLeuProTyrGluPhePheSerGluGluAsnAla                              151015                                                                        ProLysTrpArgGlyLeuLeuValProAlaLeuLysLysValGlnGly                              202530                                                                        GlnValHisProThrLeuGluSerAsnAspAspAlaLeuGlnTyrVal                              354045                                                                        GluGluLeuIleLeuGlnLeuLeuAsnMetLeuCysGlnAlaGlnPro                              505560                                                                        ArgSerAlaSerAspValGluGluArgValGlnLysSerPheProHis                              65707580                                                                      ProIleAspLysTrpAlaIleAlaAspAlaGlnSerAlaIleGluLys                              859095                                                                        ArgLysArgArgAsnProLeuSerLeuProAlaGluArgIleHisHis                              100105110                                                                     LeuLeuArgGluValLeuGlyTyrLysIleAspHisGlnValSerVal                              115120125                                                                     TyrIleValAlaValLeuGluTyrIleSerAlaAspIleLeuLysLeu                              130135140                                                                     ValGlyAsnTyrValArgAsnIleArgHisTyrGluIleThrLysGln                              145150155160                                                                  AspIleLysValAlaMetCysAlaAspLysValLeuMetAspMetPhe                              165170175                                                                     HisGlnAspValGluAspIleAsnIleLeuSerLeuThrAspGluGlu                              180185190                                                                     ProSerThrSerGlyGluGlnThrTyrTyrAspLeuValLysAlaPhe                              195200205                                                                     MetAlaGluIleArgGlnTyrIleArgGluLeuAsnLeuIleIleLys                              210215220                                                                     ValPheArgGluProPheValSerAsnSerLysLeuPheSerSerAsn                              225230235240                                                                  AspValGluAsnIlePheSerArgIleValAspIleHisGluLeuSer                              245250255                                                                     ValLysLeuLeuGlyHisIleGluAspThrValGluMetThrAspGlu                              260265270                                                                     GlySerProHisProLeuValGlySerCysPheGluAspLeuAlaGlu                              275280285                                                                     GluLeuAlaPheAspProTyrGluSerTyrAlaArgAspIleLeuArg                              290295300                                                                     ProGlyPheHisGlyHisPheLeuSerGlnLeuSerLysProGlyAla                              305310315320                                                                  AlaLeuTyrLeuGlnSerIleGlyGluGlyPheLysGluAlaValGln                              325330335                                                                     TyrValLeuProArgLeuLeuLeuAlaProValTyrHisCysLeuHis                              340345350                                                                     TyrPheGluLeuLeuLysGlnLeuGluGluLysSerGluAspGlnGlu                              355360365                                                                     AspLysGluCysMetLysGlnAlaIleThrAlaLeuLeuAsnValGln                              370375380                                                                     SerGlyMetGluLysIleCysSerLysSerLeuAlaLysArgArgLeu                              385390395400                                                                  SerGluSerAlaCysArgPheTyrSerGlnGlnMetLysGlyLysGln                              405410415                                                                     LeuAlaIleLysLysMetAsnGluIleGlnLysAsnIleAspGlyTrp                              420425430                                                                     GluGlyLysAspIleGlyGlnCysCysAsnGluPheIleMetGluGly                              435440445                                                                     ThrLeuThrArgValGlyAlaLysHisGluArgHisIlePheLeuPhe                              450455460                                                                     AspGlyLeuMetIleCysCysLysSerAsnHisGlyGlnProArgLeu                              465470475480                                                                  ProGlyAlaSerSerAlaGluTyrArgLeuLysGluLysPhePheMet                              485490495                                                                     ArgLysValGlnIleAsnAspLysAspAspThrSerGluTyrLysHis                              500505510                                                                     AlaPheGluIleIleLeuLysAspGlyAsnSerValIlePheSerAla                              515520525                                                                     LysSerAlaGluGluLysAsnAsnTrpMetAlaAlaLeuIleSerLeu                              530535540                                                                     GlnTyrArgSerThrLeuGluArgMetLeuAspValThrValLeuGln                              545550555560                                                                  GluGluLysGluGluGlnMetArgLeuProSerAlaGluValTyrArg                              565570575                                                                     PheAlaGluProAspSerGluGluAsnIleLeuPheGluGluAsnVal                              580585590                                                                     GlnProLysAlaGlyIleProIleIleLysAlaGlyThrValLeuLys                              595600605                                                                     LeuIleGluArgLeuThrTyrHisMetTyrAlaAspProAsnPheVal                              610615620                                                                     ArgThrPheLeuThrThrTyrArgSerPheCysArgProGlnGluLeu                              625630635640                                                                  LeuSerLeuLeuIleGluArgPheGluIleProGluProGluProThr                              645650655                                                                     GluAlaAspArgIleAlaIleGluAsnGlyAspGlnProLeuSerAla                              660665670                                                                     GluLeuLysArgPheArgLysGluTyrIleGlnProValGlnLeuArg                              675680685                                                                     ValLeuAsnValCysArgHisTrpValGluHisHisPheTyrAspPhe                              690695700                                                                     GluArgAspAlaAspLeuLeuGlnArgMetGluGluPheIleGlyThr                              705710715720                                                                  ValArgGlyLysAlaMetLysLysTrpValGluSerIleThrLysIle                              725730735                                                                     IleGlnArgLysLysIleAlaArgAspAsnGlyProGlyHisAsnIle                              740745750                                                                     ThrPheGlnSerSerProProThrValGluTrpHisIleSerArgPro                              755760765                                                                     GlyHisIleGluThrPheAspLeuLeuThrLeuHisProIleGluIle                              770775780                                                                     AlaArgGlnLeuThrLeuLeuGluSerAspLeuTyrArgAlaValGln                              785790795800                                                                  ProSerGluLeuValGlySerValTrpThrLysGluAspLysGluIle                              805810815                                                                     AsnSerProAsnLeuLeuLysMetIleArgHisThrThrAsnLeuThr                              820825830                                                                     LeuTrpPheGluLysCysIleValGluThrGluAsnLeuGluGluArg                              835840845                                                                     ValAlaValValSerArgIleIleGluIleLeuGlnValPheGlnGlu                              850855860                                                                     LeuAsnAsnPheAsnGlyValLeuGluValValSerAlaMetAsnSer                              865870875880                                                                  SerProValTyrArgLeuAspHisThrPheGluGlnIleProSerArg                              885890895                                                                     GlnLysLysIleLeuGluGluAlaHisGluLeuSerGluAspHisTyr                              900905910                                                                     LysLysTyrLeuAlaLysLeuArgSerIleAsnProProCysValPro                              915920925                                                                     PhePheGlyIleTyrLeuThrAsnIleLeuLysThrGluGluGlyAsn                              930935940                                                                     ProGluValLeuArgArgHisGlyLysGluLeuIleAsnPheSerLys                              945950955960                                                                  ArgArgArgValAlaGluIleThrGlyGluIleGlnGlnTyrGlnAsn                              965970975                                                                     GlnProTyrCysLeuArgValGluProAspIleLysArgPhePheGlu                              980985990                                                                     AsnLeuAsnProMetGlyAsnSerMetGluLysGluPheThrAspTyr                              99510001005                                                                   LeuPheAsnLysSerLeuGluIleGluProArgHisProLysProLeu                              101010151020                                                                  ProArgPheProLysLysTyrSerTyrProLeuLysSerProGlyVal                              1025103010351040                                                              ArgProSerAsnProArgProGlyThrMetArgHisProThrProLeu                              104510501055                                                                  GlnGlnGluProArgLysIleSerTyrSerArgIleProGluSerGlu                              106010651070                                                                  ThrGluSerThrAlaSerAlaProAsnSerProArgThrProLeuThr                              107510801085                                                                  ProProProAlaSerGlyThrSerSerAsnThrAspValCysSerVal                              109010951100                                                                  PheAspSerAspHisSerAlaSerProPheHisSerArgSerAlaSer                              1105111011151120                                                              ValSerSerIleSerLeuSerLysGlyThrAspGluValProValPro                              112511301135                                                                  ProProValProProArgArgArgProGluSerAlaProAlaGluSer                              114011451150                                                                  SerProSerLysIleMetSerLysHisLeuAspSerProProAlaIle                              115511601165                                                                  ProProArgGlnProThrSerLysAlaTyrSerProArgTyrSerIle                              117011751180                                                                  SerAspArgThrSerIleSerAspProProGluSerProProLeuLeu                              1185119011951200                                                              ProProArgGluProValArgThrProAspValPheSerSerSerPro                              120512101215                                                                  LeuHisLeuGlnProProProLeuGlyLysLysSerAspHisGlyAsn                              122012251230                                                                  AlaPhePheProAsnSerProSerProPheThrProProProProGln                              123512401245                                                                  ThrProSerProHisGlyThrArgArgHisLeuProSerProProLeu                              125012551260                                                                  ThrGlnGluMetAspLeuHisSerIleAlaGlyProProValProPro                              1265127012751280                                                              ArgGlnSerThrSerGlnLeuIleProLysLeuProProLysThrTyr                              128512901295                                                                  LysArgGluHisThrHisProSerMetHisArgAspGlyProProLeu                              130013051310                                                                  LeuGluAsnAlaHisSerSer                                                         1315                                                                          (2) INFORMATION FOR SEQ ID NO:3:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 5253 base pairs                                                   (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: DNA (genomic)                                             (ix) FEATURE:                                                                 (A) NAME/KEY: CDS                                                             (B) LOCATION: 1..3891                                                         (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:                                       CCCACCCTCTCAGCTAATGAAGAGTCTCTCTATTATATTGAAGAACTG48                            ProThrLeuSerAlaAsnGluGluSerLeuTyrTyrIleGluGluLeu                              151015                                                                        ATTTTTCAGCTGCTTAATAAGCTATGCATGGCTCAACCAAGGACTGTT96                            IlePheGlnLeuLeuAsnLysLeuCysMetAlaGlnProArgThrVal                              202530                                                                        CAAGATGTTGAGGAACGAGTTCAAAAGACCTTTCCTCATCCTATTGAT144                           GlnAspValGluGluArgValGlnLysThrPheProHisProIleAsp                              354045                                                                        AAATGGGCAATTGCTGATGCACAATCTGCTATAGAGAAACGAAAACGA192                           LysTrpAlaIleAlaAspAlaGlnSerAlaIleGluLysArgLysArg                              505560                                                                        AGAAATCCTCTCTTACTACCTGTGGACAAAATCCATCCTTCCTTGAAG240                           ArgAsnProLeuLeuLeuProValAspLysIleHisProSerLeuLys                              65707580                                                                      GAAGTTTTGGGGTATAAAGTGGACTACCATGTGTCCCTCTACATTGTG288                           GluValLeuGlyTyrLysValAspTyrHisValSerLeuTyrIleVal                              859095                                                                        GCTGTATTGGAGTATATCTCAGCAGATATTTTGAAATTGGCTGGTAAT336                           AlaValLeuGluTyrIleSerAlaAspIleLeuLysLeuAlaGlyAsn                              100105110                                                                     TATGTTTTTAATATCCGGCATTATGAAATATCTCAGCAAGACATTAAA384                           TyrValPheAsnIleArgHisTyrGluIleSerGlnGlnAspIleLys                              115120125                                                                     GTGTCCATGTGTGCAGATAAGGTTTTGATGGACATGTTCGATCAGGAT432                           ValSerMetCysAlaAspLysValLeuMetAspMetPheAspGlnAsp                              130135140                                                                     GATGATATAGGCTTGGTTTCTCTCTGTGAAGATGAGCCTTGTTCTTCT480                           AspAspIleGlyLeuValSerLeuCysGluAspGluProCysSerSer                              145150155160                                                                  GGTGAGCTAAACTATTATGACCTCGTCAGGACTGAAATTGCAGAAGAA528                           GlyGluLeuAsnTyrTyrAspLeuValArgThrGluIleAlaGluGlu                              165170175                                                                     AGACAGTATCTACGGGAGCTGAATATGATCATTAAAGTGTTCCGGGAA576                           ArgGlnTyrLeuArgGluLeuAsnMetIleIleLysValPheArgGlu                              180185190                                                                     GCCTTTCTCTTGGACAGAAAGTTGTTCAAGCCTTCTGAAATTGAAAAG624                           AlaPheLeuLeuAspArgLysLeuPheLysProSerGluIleGluLys                              195200205                                                                     ATTTTCAGTAACATTTCAGATATACATGAATTGACTGTGAAACTTTTA672                           IlePheSerAsnIleSerAspIleHisGluLeuThrValLysLeuLeu                              210215220                                                                     GGTTTAATTGAAGACACAGTAGAAATGACAGATGAAAGTAGTCCTCAT720                           GlyLeuIleGluAspThrValGluMetThrAspGluSerSerProHis                              225230235240                                                                  CCATTAGCTGGTAGCTGTTTTGAAGATTTAGCAGAGGAGCAAGCGTTT768                           ProLeuAlaGlySerCysPheGluAspLeuAlaGluGluGlnAlaPhe                              245250255                                                                     GATCCCTATGAAACATTATCACAGGACATTCTTGCACCAGAGTTTAAT816                           AspProTyrGluThrLeuSerGlnAspIleLeuAlaProGluPheAsn                              260265270                                                                     GACCACTTCAGCAAGTTGATGGCCAGACCTGCAGTCGCTCTACATTTT864                           AspHisPheSerLysLeuMetAlaArgProAlaValAlaLeuHisPhe                              275280285                                                                     CAGTCCATTGCTGACGGCTTTAAGGAGGCTGTTCGTTATGTCCTTCCA912                           GlnSerIleAlaAspGlyPheLysGluAlaValArgTyrValLeuPro                              290295300                                                                     CGCCTCATGCTGGTTCCCGTGTATCACTGTTGGCATTACTTTGAATTA960                           ArgLeuMetLeuValProValTyrHisCysTrpHisTyrPheGluLeu                              305310315320                                                                  TTAAAGTTGAAGGCATGCAGTGAAGAGCAGGAGGACAAAGAGTGTTTG1008                          LeuLysLeuLysAlaCysSerGluGluGlnGluAspLysGluCysLeu                              325330335                                                                     AATCAGGCTATAACTGCCCTCATGAACCTCCAAGGCAGCATGGACCGC1056                          AsnGlnAlaIleThrAlaLeuMetAsnLeuGlnGlySerMetAspArg                              340345350                                                                     ATTTACAAGCAGCACTCCCCCAGACGCCGGCCTGGGGATCCAGTTTGC1104                          IleTyrLysGlnHisSerProArgArgArgProGlyAspProValCys                              355360365                                                                     CTTTTTTACAATCGTCAATTAAGAAGCAAACACCTGGCTATCAAAAAA1152                          LeuPheTyrAsnArgGlnLeuArgSerLysHisLeuAlaIleLysLys                              370375380                                                                     ATGAATGAAATTCAGAAAAACATAGATGGGTGGGAAGGCAAAGATATC1200                          MetAsnGluIleGlnLysAsnIleAspGlyTrpGluGlyLysAspIle                              385390395400                                                                  GGACAGTGTTGTAATGAGTTCATAATGGAGGGGCCACTGACCAGAATT1248                          GlyGlnCysCysAsnGluPheIleMetGluGlyProLeuThrArgIle                              405410415                                                                     GGTGCTAAACACGAAAGGCATATCTTTCTCTTTGATGGCTTAATGATC1296                          GlyAlaLysHisGluArgHisIlePheLeuPheAspGlyLeuMetIle                              420425430                                                                     AGCTGTAAACCCAATCATGGCCAGACCCGGCTTCCAGGATATAGCAGT1344                          SerCysLysProAsnHisGlyGlnThrArgLeuProGlyTyrSerSer                              435440445                                                                     GCAGAATACAGATTAAAGGAGAAGTTTGTCATGAGGAAAATTCAAATC1392                          AlaGluTyrArgLeuLysGluLysPheValMetArgLysIleGlnIle                              450455460                                                                     TGTGATAAGGAAGACGCCTGTGAGTACAGACATGCTTTTGAATTAGTG1440                          CysAspLysGluAspAlaCysGluTyrArgHisAlaPheGluLeuVal                              465470475480                                                                  TCCAAAGATGAAAACAGTGTAATATTTGCTGCCAAATCAGCTGAAGAG1488                          SerLysAspGluAsnSerValIlePheAlaAlaLysSerAlaGluGlu                              485490495                                                                     AAAAACAACTGGATGGCAGCCCTCATTTCCCTGCACTATCGCAGCACT1536                          LysAsnAsnTrpMetAlaAlaLeuIleSerLeuHisTyrArgSerThr                              500505510                                                                     CTAGACAGAATGCTGGACTCTGTGCTGCTGAAAGAAGAGAATGAGCAG1584                          LeuAspArgMetLeuAspSerValLeuLeuLysGluGluAsnGluGln                              515520525                                                                     CCCCTGAGGCTACCCAGTCCAGATATGTATCGCTTTGTGGTAACAGAC1632                          ProLeuArgLeuProSerProAspMetTyrArgPheValValThrAsp                              530535540                                                                     TCTGAGGAAAACATTGTGTTTGAAGACAACTTGCAAAGCAGAAGTGGG1680                          SerGluGluAsnIleValPheGluAspAsnLeuGlnSerArgSerGly                              545550555560                                                                  ATCCCCATAATTAAAGGAGGCACTGTGGTGAAGTTGATCGAAAGGCTA1728                          IleProIleIleLysGlyGlyThrValValLysLeuIleGluArgLeu                              565570575                                                                     ACATACCACATGTATGCAGATCCCAATTTTGTTCGTACTTTTCTTACT1776                          ThrTyrHisMetTyrAlaAspProAsnPheValArgThrPheLeuThr                              580585590                                                                     ACATATCGTTCATTTTGTAAACCACAGGAATTGCTAAACTTGCTGATA1824                          ThrTyrArgSerPheCysLysProGlnGluLeuLeuAsnLeuLeuIle                              595600605                                                                     GAACGGTTTGAAATTCCAGAACCAGAACCTACTGAGGCAGACAAGCTG1872                          GluArgPheGluIleProGluProGluProThrGluAlaAspLysLeu                              610615620                                                                     GCGTTAGAAAAAGGCGAGCAGCCAATCAGCGCAGATCTGAAAAGATTC1920                          AlaLeuGluLysGlyGluGlnProIleSerAlaAspLeuLysArgPhe                              625630635640                                                                  CGCAAGGAATACGTCCAACCTGTGCAGCTTAGGGTCTTGAATGTCTTT1968                          ArgLysGluTyrValGlnProValGlnLeuArgValLeuAsnValPhe                              645650655                                                                     CGCCACTGGGTTGAGCATCATTATTATGACTTTGAAAGAGACTTGGAA2016                          ArgHisTrpValGluHisHisTyrTyrAspPheGluArgAspLeuGlu                              660665670                                                                     CTGCTTGAAAGACTAGAATCCTTCATTTCAAGTGTAAGAGGGAAAGCC2064                          LeuLeuGluArgLeuGluSerPheIleSerSerValArgGlyLysAla                              675680685                                                                     ATGAAGAAATGGGTAGAATCCATTGCTAAAATAATCAAGAGGAAGAAG2112                          MetLysLysTrpValGluSerIleAlaLysIleIleLysArgLysLys                              690695700                                                                     CAAGCTCAGGCAAATGGAATAAGCCATAATATCACCTTTGAAAGTTCC2160                          GlnAlaGlnAlaAsnGlyIleSerHisAsnIleThrPheGluSerSer                              705710715720                                                                  CCCCCACCAGTGGAATGGCACATCAGTAGAACAGGACAGTTCGAAACA2208                          ProProProValGluTrpHisIleSerArgThrGlyGlnPheGluThr                              725730735                                                                     TTTGACCTTATGACACTTCATCCAATAGAGATCGCACGGCAGCTAACA2256                          PheAspLeuMetThrLeuHisProIleGluIleAlaArgGlnLeuThr                              740745750                                                                     CTTTTGGAATCTGACCTCTACAGGAAAGTCCAGCCCTCTGAACTTGTA2304                          LeuLeuGluSerAspLeuTyrArgLysValGlnProSerGluLeuVal                              755760765                                                                     GGGAGTGTCTGGACCAAAGAAGATAAAGAAATAAATTCTCCAAACTTA2352                          GlySerValTrpThrLysGluAspLysGluIleAsnSerProAsnLeu                              770775780                                                                     TTAAAAATGATTCGCCATACAACAAACCTCACTCTATGGTTTGAGAAA2400                          LeuLysMetIleArgHisThrThrAsnLeuThrLeuTrpPheGluLys                              785790795800                                                                  TGCATTGTGGAAGCAGAAAACTTTGAAGAACGGGTGGCAGTGCTCAGC2448                          CysIleValGluAlaGluAsnPheGluGluArgValAlaValLeuSer                              805810815                                                                     AGAATAGTAGAAATTCTGCAAGTATTTCAAGACTTGAATAATTTCAAT2496                          ArgIleValGluIleLeuGlnValPheGlnAspLeuAsnAsnPheAsn                              820825830                                                                     GGCGTGTTGGAGATAGTGAGTGCAGTCAACTCCGTGTCAGTGTACAGG2544                          GlyValLeuGluIleValSerAlaValAsnSerValSerValTyrArg                              835840845                                                                     CTAGACCACACGTTTGAGGCACTGCAGGAAAGGAAGCGGAGAATTTTG2592                          LeuAspHisThrPheGluAlaLeuGlnGluArgLysArgArgIleLeu                              850855860                                                                     GATGACGCTGTGGAACTAAGTCAGGACCACTTTAAAAAGTACCTAGTA2640                          AspAspAlaValGluLeuSerGlnAspHisPheLysLysTyrLeuVal                              865870875880                                                                  AAACTTAAGTCAATCAATCCGCCTTGTGTGCCTTTTTTTGGAATATAT2688                          LysLeuLysSerIleAsnProProCysValProPhePheGlyIleTyr                              885890895                                                                     TTAACAAATATTCTGAAGACTGAAGAAGGGAACAGTGACTTTCTAAAG2736                          LeuThrAsnIleLeuLysThrGluGluGlyAsnSerAspPheLeuLys                              900905910                                                                     AGGAAAGGGAAAGATTTGATCAATTTCAGTAAGAGGAGGAAAGTGGCT2784                          ArgLysGlyLysAspLeuIleAsnPheSerLysArgArgLysValAla                              915920925                                                                     GAAATAACTGGAGAGATCCAGCAGTATCAGAACCAACCGTACTGCTTA2832                          GluIleThrGlyGluIleGlnGlnTyrGlnAsnGlnProTyrCysLeu                              930935940                                                                     CGGACAGAACCAGAAATGAGGAGATTCTTTGAAAACCTCAACCCCATG2880                          ArgThrGluProGluMetArgArgPhePheGluAsnLeuAsnProMet                              945950955960                                                                  GGAATTTTATCTGAAAAAGAGTTTACAGATTATTTGTTCAACAAATCA2928                          GlyIleLeuSerGluLysGluPheThrAspTyrLeuPheAsnLysSer                              965970975                                                                     TTAGAAATCGAACCCCGAAACTGCAAACAACCACCTCGATTTCCTAGG2976                          LeuGluIleGluProArgAsnCysLysGlnProProArgPheProArg                              980985990                                                                     AAGTCAACCTTTTCCTTAAAATCTCCTGGAATAAGGCCCAATGCTGGC3024                          LysSerThrPheSerLeuLysSerProGlyIleArgProAsnAlaGly                              99510001005                                                                   CGCCATGGCTCTACCTCAGGCACGCTACGAGGTCACCCAACGCCTCTG3072                          ArgHisGlySerThrSerGlyThrLeuArgGlyHisProThrProLeu                              101010151020                                                                  GAAAGAGAGCCTTATAAGATAAGCTTTAGCCGGATCGCTGAGACAGAG3120                          GluArgGluProTyrLysIleSerPheSerArgIleAlaGluThrGlu                              1025103010351040                                                              CTAGAATCAACAGTGTCTGCACCAACCTCCCCCAACACTCCATCCACC3168                          LeuGluSerThrValSerAlaProThrSerProAsnThrProSerThr                              104510501055                                                                  CCACCAGTGTCTGCTTCTTCAGACCACAGCGTGTTTCTAGATGTGGAC3216                          ProProValSerAlaSerSerAspHisSerValPheLeuAspValAsp                              106010651070                                                                  CTCAATAGCTCCTGTGGCAGCAACACCATCTTTGCTCCAGTCCTCTTG3264                          LeuAsnSerSerCysGlySerAsnThrIlePheAlaProValLeuLeu                              107510801085                                                                  CCACACTCAAAGACTTTCTTCAGCTCATGTGGAAGTTTACACAAACTG3312                          ProHisSerLysThrPhePheSerSerCysGlySerLeuHisLysLeu                              109010951100                                                                  AGTGAAGAGCCACTAATTCCTCCTCCGCTTCCCCCTCGGAAAAAGTTT3360                          SerGluGluProLeuIleProProProLeuProProArgLysLysPhe                              1105111011151120                                                              GATCATGATGCTCTCAATTCCAAGGGAGCTGTGAAATCTGATGATGAC3408                          AspHisAspAlaLeuAsnSerLysGlyAlaValLysSerAspAspAsp                              112511301135                                                                  CCTCCTGCTATTCCACCAAGACAGCCCCCTCCTCCGAAGGTAAAGCCA3456                          ProProAlaIleProProArgGlnProProProProLysValLysPro                              114011451150                                                                  AGAGTTCCTGTCCTCATGGGTACATTTGATGGGCCTGTGCCCAGTCCA3504                          ArgValProValLeuMetGlyThrPheAspGlyProValProSerPro                              115511601165                                                                  CCTCCACCTCCTCCAAGAGACCCTCTTCCTGATACCCCTCCACCAGTT3552                          ProProProProProArgAspProLeuProAspThrProProProVal                              117011751180                                                                  CCTCTTCGGCCTCCGGAACACTTTATAAACTGTCCATTTAATCTTCAG3600                          ProLeuArgProProGluHisPheIleAsnCysProPheAsnLeuGln                              1185119011951200                                                              CCGCCTCCACTGGGCCATCCTCACAGAGACCCAGACTGGCTCAGAGAC3648                          ProProProLeuGlyHisProHisArgAspProAspTrpLeuArgAsp                              120512101215                                                                  GTCAGCACGTGTCCTAACTCACCAAGCACTCCTCCCACTACGCCCTCT3696                          ValSerThrCysProAsnSerProSerThrProProThrThrProSer                              122012251230                                                                  CCACGGATTCCACGCAGCTGTCACTTGCTCAGCTCCAGTCACAGCAGC3744                          ProArgIleProArgSerCysHisLeuLeuSerSerSerHisSerSer                              123512401245                                                                  CTTGCTCATCTTCCAGCTCCTCCTGTCCCACCAAGGCAGAATTCAAGC3792                          LeuAlaHisLeuProAlaProProValProProArgGlnAsnSerSer                              125012551260                                                                  CCTCTCTTACCAAAGCTGCCACCAAAGACTTACAAACGGGAGCTTTCC3840                          ProLeuLeuProLysLeuProProLysThrTyrLysArgGluLeuSer                              1265127012751280                                                              CACCCGCCACTGTATAGACTGCCTCTGCTGGAAAATGCAGAAACTCCT3888                          HisProProLeuTyrArgLeuProLeuLeuGluAsnAlaGluThrPro                              128512901295                                                                  CAATGACCTTGGCCATATGTAGTCATTGACACTGGAATAGTATTTGTAAAGGT3941                     Gln                                                                           TTTTAATTTATTCAAAAAGACATAGTATTTTAGTACTTTTTACAGAAATGCTACTGATTA4001              AATAAGCTCTTAAGAATTAGTAAACTTGTTGGATGGCAGTGGCCCACAGCTGTAATCCCA4061              GCACCCTGGTTGCAGGGGCAGTGGGCTTCAGGGTTTGAGAGCAGCCTGGTCTACAGAGCA4121              AGTCCCAGGACAGCCAGGGCTACACAAAAAAACCTTGTCTCAAAAGTCAAAATACAAACA4181              AAAGAGAGAAAAGGAAGGAAGGAAAGAATTTGAAATATTAAAATGCAAAAGCCCTTCACC4241              ATAGCCCCCAGGTGATCAGCAGCATTGCTTCCTCGGCTCCTCAGTGCTGCCCTAGGCCAG4301              TATAAAGACTGTATTGCACTGTAGACTCTGCTAGCAGACGGCACTGAGAGGAGCCAGCGC4361              TCGAGGGCCGTTCTCACGCCTGACTGATAGATACCTTTTTAGGGTGATGAACTTACACAG4421              ATGCAGAAGATATGGGGTGGTGGTCCTGGGTTTTAACCCTCTGACCGTCTTCTAGCTTCT4481              AATTTTGTTTGGTTTTTACATCTAGGAGACTTAGGAATAATACCCGCTGTTCTTAAACTC4541              TTTGAGACCATGTCTTAAATGTCAGTATTTGCTGCTGAAGACAAAAACGGAAAATAGAAT4601              GAAATAATAGAATGCACTGTGTTTATTATTTTGTTAAAATTATAAACAGTTCTACATAAC4661              CTGATTATAGAAGAAGGGCATGTGTTCATTAAGATGTGCCTTTTGTTTTGCAGTGTATGG4721              TGTTTAGCTAATCATTGTTTAGCTAATGATTTGCCTATTATTTGGGAAGACAAAATTAAT4781              ATGCCATATATGTACAGTTTATTTATATTGTATATATTTAAAGATAATGCTAATAACCTC4841              TATAAATGTAAGTGACTTGAGGCCTATAATACAATCTGCTATTTGACTAATTTGTAAGTC4901              TGGAACAAAAGTGTCTTATGGCATAAGAACCAACTGCCATTGTCAAACCTATTAACTGTC4961              TTTAATCTCGTGTTAACTGAAATTTTTGAAAAGTTTTTCCAGATTAGTAATATTTAAACA5021              GAAAATACTTTAAAAAGCTTTATTAAATTTTTTAATCAGACAGGATAAAGCTTTGCCATT5081              TGGATACTATCATTCAAAGTGATCAAGGTATGTATGTTATGCTGATAGTGCAGTAGCAGC5141              CATTGTAAAGTAGCCAAAAGCCACGTTGTTTATCTACTGGTCTGTGGCCTTTTACTGTGC5201              TTTGTATCAGAGTTCTTAACAAGATTAATAAATCACCTCAGTCTTAATTTGT5253                      (2) INFORMATION FOR SEQ ID NO:4:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 1297 amino acids                                                  (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: protein                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:                                       ProThrLeuSerAlaAsnGluGluSerLeuTyrTyrIleGluGluLeu                              151015                                                                        IlePheGlnLeuLeuAsnLysLeuCysMetAlaGlnProArgThrVal                              202530                                                                        GlnAspValGluGluArgValGlnLysThrPheProHisProIleAsp                              354045                                                                        LysTrpAlaIleAlaAspAlaGlnSerAlaIleGluLysArgLysArg                              505560                                                                        ArgAsnProLeuLeuLeuProValAspLysIleHisProSerLeuLys                              65707580                                                                      GluValLeuGlyTyrLysValAspTyrHisValSerLeuTyrIleVal                              859095                                                                        AlaValLeuGluTyrIleSerAlaAspIleLeuLysLeuAlaGlyAsn                              100105110                                                                     TyrValPheAsnIleArgHisTyrGluIleSerGlnGlnAspIleLys                              115120125                                                                     ValSerMetCysAlaAspLysValLeuMetAspMetPheAspGlnAsp                              130135140                                                                     AspAspIleGlyLeuValSerLeuCysGluAspGluProCysSerSer                              145150155160                                                                  GlyGluLeuAsnTyrTyrAspLeuValArgThrGluIleAlaGluGlu                              165170175                                                                     ArgGlnTyrLeuArgGluLeuAsnMetIleIleLysValPheArgGlu                              180185190                                                                     AlaPheLeuLeuAspArgLysLeuPheLysProSerGluIleGluLys                              195200205                                                                     IlePheSerAsnIleSerAspIleHisGluLeuThrValLysLeuLeu                              210215220                                                                     GlyLeuIleGluAspThrValGluMetThrAspGluSerSerProHis                              225230235240                                                                  ProLeuAlaGlySerCysPheGluAspLeuAlaGluGluGlnAlaPhe                              245250255                                                                     AspProTyrGluThrLeuSerGlnAspIleLeuAlaProGluPheAsn                              260265270                                                                     AspHisPheSerLysLeuMetAlaArgProAlaValAlaLeuHisPhe                              275280285                                                                     GlnSerIleAlaAspGlyPheLysGluAlaValArgTyrValLeuPro                              290295300                                                                     ArgLeuMetLeuValProValTyrHisCysTrpHisTyrPheGluLeu                              305310315320                                                                  LeuLysLeuLysAlaCysSerGluGluGlnGluAspLysGluCysLeu                              325330335                                                                     AsnGlnAlaIleThrAlaLeuMetAsnLeuGlnGlySerMetAspArg                              340345350                                                                     IleTyrLysGlnHisSerProArgArgArgProGlyAspProValCys                              355360365                                                                     LeuPheTyrAsnArgGlnLeuArgSerLysHisLeuAlaIleLysLys                              370375380                                                                     MetAsnGluIleGlnLysAsnIleAspGlyTrpGluGlyLysAspIle                              385390395400                                                                  GlyGlnCysCysAsnGluPheIleMetGluGlyProLeuThrArgIle                              405410415                                                                     GlyAlaLysHisGluArgHisIlePheLeuPheAspGlyLeuMetIle                              420425430                                                                     SerCysLysProAsnHisGlyGlnThrArgLeuProGlyTyrSerSer                              435440445                                                                     AlaGluTyrArgLeuLysGluLysPheValMetArgLysIleGlnIle                              450455460                                                                     CysAspLysGluAspAlaCysGluTyrArgHisAlaPheGluLeuVal                              465470475480                                                                  SerLysAspGluAsnSerValIlePheAlaAlaLysSerAlaGluGlu                              485490495                                                                     LysAsnAsnTrpMetAlaAlaLeuIleSerLeuHisTyrArgSerThr                              500505510                                                                     LeuAspArgMetLeuAspSerValLeuLeuLysGluGluAsnGluGln                              515520525                                                                     ProLeuArgLeuProSerProAspMetTyrArgPheValValThrAsp                              530535540                                                                     SerGluGluAsnIleValPheGluAspAsnLeuGlnSerArgSerGly                              545550555560                                                                  IleProIleIleLysGlyGlyThrValValLysLeuIleGluArgLeu                              565570575                                                                     ThrTyrHisMetTyrAlaAspProAsnPheValArgThrPheLeuThr                              580585590                                                                     ThrTyrArgSerPheCysLysProGlnGluLeuLeuAsnLeuLeuIle                              595600605                                                                     GluArgPheGluIleProGluProGluProThrGluAlaAspLysLeu                              610615620                                                                     AlaLeuGluLysGlyGluGlnProIleSerAlaAspLeuLysArgPhe                              625630635640                                                                  ArgLysGluTyrValGlnProValGlnLeuArgValLeuAsnValPhe                              645650655                                                                     ArgHisTrpValGluHisHisTyrTyrAspPheGluArgAspLeuGlu                              660665670                                                                     LeuLeuGluArgLeuGluSerPheIleSerSerValArgGlyLysAla                              675680685                                                                     MetLysLysTrpValGluSerIleAlaLysIleIleLysArgLysLys                              690695700                                                                     GlnAlaGlnAlaAsnGlyIleSerHisAsnIleThrPheGluSerSer                              705710715720                                                                  ProProProValGluTrpHisIleSerArgThrGlyGlnPheGluThr                              725730735                                                                     PheAspLeuMetThrLeuHisProIleGluIleAlaArgGlnLeuThr                              740745750                                                                     LeuLeuGluSerAspLeuTyrArgLysValGlnProSerGluLeuVal                              755760765                                                                     GlySerValTrpThrLysGluAspLysGluIleAsnSerProAsnLeu                              770775780                                                                     LeuLysMetIleArgHisThrThrAsnLeuThrLeuTrpPheGluLys                              785790795800                                                                  CysIleValGluAlaGluAsnPheGluGluArgValAlaValLeuSer                              805810815                                                                     ArgIleValGluIleLeuGlnValPheGlnAspLeuAsnAsnPheAsn                              820825830                                                                     GlyValLeuGluIleValSerAlaValAsnSerValSerValTyrArg                              835840845                                                                     LeuAspHisThrPheGluAlaLeuGlnGluArgLysArgArgIleLeu                              850855860                                                                     AspAspAlaValGluLeuSerGlnAspHisPheLysLysTyrLeuVal                              865870875880                                                                  LysLeuLysSerIleAsnProProCysValProPhePheGlyIleTyr                              885890895                                                                     LeuThrAsnIleLeuLysThrGluGluGlyAsnSerAspPheLeuLys                              900905910                                                                     ArgLysGlyLysAspLeuIleAsnPheSerLysArgArgLysValAla                              915920925                                                                     GluIleThrGlyGluIleGlnGlnTyrGlnAsnGlnProTyrCysLeu                              930935940                                                                     ArgThrGluProGluMetArgArgPhePheGluAsnLeuAsnProMet                              945950955960                                                                  GlyIleLeuSerGluLysGluPheThrAspTyrLeuPheAsnLysSer                              965970975                                                                     LeuGluIleGluProArgAsnCysLysGlnProProArgPheProArg                              980985990                                                                     LysSerThrPheSerLeuLysSerProGlyIleArgProAsnAlaGly                              99510001005                                                                   ArgHisGlySerThrSerGlyThrLeuArgGlyHisProThrProLeu                              101010151020                                                                  GluArgGluProTyrLysIleSerPheSerArgIleAlaGluThrGlu                              1025103010351040                                                              LeuGluSerThrValSerAlaProThrSerProAsnThrProSerThr                              104510501055                                                                  ProProValSerAlaSerSerAspHisSerValPheLeuAspValAsp                              106010651070                                                                  LeuAsnSerSerCysGlySerAsnThrIlePheAlaProValLeuLeu                              107510801085                                                                  ProHisSerLysThrPhePheSerSerCysGlySerLeuHisLysLeu                              109010951100                                                                  SerGluGluProLeuIleProProProLeuProProArgLysLysPhe                              1105111011151120                                                              AspHisAspAlaLeuAsnSerLysGlyAlaValLysSerAspAspAsp                              112511301135                                                                  ProProAlaIleProProArgGlnProProProProLysValLysPro                              114011451150                                                                  ArgValProValLeuMetGlyThrPheAspGlyProValProSerPro                              115511601165                                                                  ProProProProProArgAspProLeuProAspThrProProProVal                              117011751180                                                                  ProLeuArgProProGluHisPheIleAsnCysProPheAsnLeuGln                              1185119011951200                                                              ProProProLeuGlyHisProHisArgAspProAspTrpLeuArgAsp                              120512101215                                                                  ValSerThrCysProAsnSerProSerThrProProThrThrProSer                              122012251230                                                                  ProArgIleProArgSerCysHisLeuLeuSerSerSerHisSerSer                              123512401245                                                                  LeuAlaHisLeuProAlaProProValProProArgGlnAsnSerSer                              125012551260                                                                  ProLeuLeuProLysLeuProProLysThrTyrLysArgGluLeuSer                              1265127012751280                                                              HisProProLeuTyrArgLeuProLeuLeuGluAsnAlaGluThrPro                              128512901295                                                                  Gln                                                                           (2) INFORMATION FOR SEQ ID NO:5:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 1572 amino acids                                                  (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: protein                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:                                       MetPheSerGlyProSerGlyHisAlaHisThrIleSerTyrGlyGly                              151015                                                                        GlyIleGlyLeuGlyThrGlyGlyGlyGlyGlySerGlyGlySerGly                              202530                                                                        SerGlySerGlnGlyGlyGlyGlyGlyIleGlyIleGlyGlyGlyGly                              354045                                                                        ValAlaGlyLeuGlnAspCysAspGlyTyrAspPheThrLysCysGlu                              505560                                                                        AsnAlaAlaArgTrpArgGlyLeuPheThrProSerLeuLysLysVal                              65707580                                                                      LeuGluGlnValHisProArgValThrAlaLysGluAspAlaLeuLeu                              859095                                                                        TyrValGluLysLeuCysLeuArgLeuLeuAlaMetLeuCysAlaLys                              100105110                                                                     ProLeuProHisSerValGlnAspValGluGluLysValAsnLysSer                              115120125                                                                     PheProAlaProIleAspGlnTrpAlaLeuAsnGluAlaLysGluVal                              130135140                                                                     IleAsnSerLysLysArgLysSerValLeuProThrGluLysValHis                              145150155160                                                                  ThrLeuLeuGlnLysAspValLeuGlnTyrLysIleAspSerSerVal                              165170175                                                                     SerAlaPheLeuValAlaValLeuGluTyrIleSerAlaAspIleLeu                              180185190                                                                     LysMetAlaGlyAspTyrValIleLysIleAlaHisCysGluIleThr                              195200205                                                                     LysGluAspIleGluValValMetAsnAlaAspArgValLeuMetAsp                              210215220                                                                     MetLeuAsnGlnSerGluAlaHisIleLeuProSerProLeuSerLeu                              225230235240                                                                  ProAlaGlnArgAlaSerAlaThrTyrGluGluThrValLysGluLeu                              245250255                                                                     IleHisAspGluLysGlnTyrGlnArgAspLeuHisMetIleIleArg                              260265270                                                                     ValPheArgGluGluLeuValLysIleValSerAspProArgGluLeu                              275280285                                                                     GluProIlePheSerAsnIleMetAspIleTyrGluValThrValThr                              290295300                                                                     LeuLeuGlySerLeuGluAspValIleGluMetSerGlnGluGlnSer                              305310315320                                                                  AlaProCysValGlySerCysPheGluGluLeuAlaGluAlaGluGlu                              325330335                                                                     PheAspValTyrLysLysTyrAlaTyrAspValThrSerGlnAlaSer                              340345350                                                                     ArgAspAlaLeuAsnAsnLeuLeuSerLysProGlyAlaSerSerLeu                              355360365                                                                     ThrThrAlaGlyHisGlyPheArgAspAlaValLysTyrTyrLeuPro                              370375380                                                                     LysLeuLeuLeuValProIleCysHisAlaPheValTyrPheAspTyr                              385390395400                                                                  IleLysHisLeuLysAspLeuSerSerSerGlnAspAspIleGluSer                              405410415                                                                     PheGluGlnValGlnGlyLeuLeuHisProLeuHisCysAspLeuGlu                              420425430                                                                     LysValMetAlaSerLeuSerLysGluArgGlnValProValSerGly                              435440445                                                                     ArgValArgArgGlnLeuAlaIleGluArgThrArgGluLeuGlnMet                              450455460                                                                     LysValGluHisTrpGluAspLysAspValGlyGlnAsnCysAsnGlu                              465470475480                                                                  PheIleArgGluAspSerLeuSerLysLeuGlySerGlyLysArgIle                              485490495                                                                     TrpSerGluArgLysValPheLeuPheAspGlyLeuMetValLeuCys                              500505510                                                                     LysAlaAsnThrLysLysGlnThrProSerAlaGlyAlaThrAlaTyr                              515520525                                                                     AspTyrArgLeuLysGluLysTyrPheMetArgArgValAspIleAsn                              530535540                                                                     AspArgProAspSerAspAspLeuLysAsnSerPheGluLeuAlaPro                              545550555560                                                                  ArgMetGlnProProIleValLeuThrAlaLysAsnAlaGlnHisLys                              565570575                                                                     HisAspTrpMetAlaAspLeuLeuMetValIleThrLysSerMetLeu                              580585590                                                                     AspArgHisLeuAspSerIleLeuGlnAspIleGluArgLysHisPro                              595600605                                                                     LeuArgMetProSerProGluIleTyrLysPheAlaValProAspSer                              610615620                                                                     GlyAspAsnIleValLeuGluGluArgGluSerAlaGlyValProMet                              625630635640                                                                  IleLysGlyAlaThrLeuCysLysLeuIleGluArgLeuThrTyrHis                              645650655                                                                     IleTyrAlaAspProThrPheValArgThrPheLeuThrThrTyrArg                              660665670                                                                     TyrPheCysSerProGlnGlnLeuLeuGlnLeuLeuValGluArgPhe                              675680685                                                                     AsnIleProAspProSerLeuValTyrGlnAspThrGlyThrAlaGly                              690695700                                                                     AlaGlyGlyMetGlyGlyValGlyGlyAspLysGluHisLysAsnSer                              705710715720                                                                  HisArgGluAspTrpLysArgTyrArgLysGluTyrValGlnProVal                              725730735                                                                     GlnPheArgValLeuAsnValLeuArgHisTrpValAspHisHisPhe                              740745750                                                                     TyrAspPheGluLysAspProMetLeuLeuGluLysLeuLeuAsnPhe                              755760765                                                                     LeuGluHisValAsnGlyLysSerMetArgLysTrpValAspSerVal                              770775780                                                                     LeuLysIleValGlnArgLysAsnGluGlnGluLysSerAsnLysLys                              785790795800                                                                  IleValTyrAlaTyrGlyHisAspProProProIleGluHisHisLeu                              805810815                                                                     SerValProAsnAspGluIleThrLeuLeuThrLeuHisProLeuGlu                              820825830                                                                     LeuAlaArgGlnLeuThrLeuLeuGluPheGluMetTyrLysAsnVal                              835840845                                                                     LysProSerGluLeuValGlySerProTrpThrLysLysAspLysGlu                              850855860                                                                     ValLysSerProAsnLeuLeuLysIleMetLysHisThrThrAsnVal                              865870875880                                                                  ThrArgTrpIleGluLysSerIleThrGluAlaGluAsnTyrGluGlu                              885890895                                                                     ArgLeuAlaIleMetGlnArgAlaIleGluValMetMetValMetLeu                              900905910                                                                     GluLeuAsnAsnPheAsnGlyIleLeuSerIleValAlaAlaMetGly                              915920925                                                                     ThrAlaSerValTyrArgLeuArgTrpThrPheGlnGlyLeuProGlu                              930935940                                                                     ArgTyrArgLysPheLeuGluGluCysArgGluLeuSerAspAspHis                              945950955960                                                                  LeuLysLysTyrGlnGluArgLeuArgSerIleAsnProProCysVal                              965970975                                                                     ProPhePheGlyArgTyrLeuThrAsnIleLeuHisLeuGluGluGly                              980985990                                                                     AsnProAspLeuLeuAlaAsnThrGluLeuIleAsnPheSerLysArg                              99510001005                                                                   ArgLysValAlaGluIleIleGlyGluIleGlnGlnTyrGlnAsnGln                              101010151020                                                                  ProTyrCysLeuAsnGluGluSerThrIleArgGlnPhePheGluGln                              1025103010351040                                                              LeuAspProPheAsnGlyLeuSerAspLysGlnMetSerAspTyrLeu                              104510501055                                                                  TyrAsnGluSerLeuArgIleGluProArgGlyCysLysThrValPro                              106010651070                                                                  LysPheProArgLysTrpProHisIleProLeuLysSerProGlyIle                              107510801085                                                                  LysProArgArgGlnAsnGlnThrAsnSerSerSerLysLeuSerAsn                              109010951100                                                                  SerThrSerSerValAlaAlaAlaAlaAlaAlaSerSerThrAlaThr                              1105111011151120                                                              SerIleAlaThrAlaSerAlaProSerLeuHisAlaSerSerIleMet                              112511301135                                                                  AspAlaProThrAlaAlaAlaAlaAsnAlaGlySerGlyThrLeuAla                              114011451150                                                                  GlyGluGlnSerProGlnHisAsnProHisAlaPheSerValPheAla                              115511601165                                                                  ProValIleIleProGluArgAsnThrSerSerTrpSerGlyThrPro                              117011751180                                                                  GlnHisThrArgThrAspGlnAsnAsnGlyGluValSerValProAla                              1185119011951200                                                              ProHisLeuProLysLysProGlyAlaHisValTrpAlaAsnAsnAsn                              120512101215                                                                  SerThrLeuAlaSerAlaSerAlaMetAspValValPheSerProAla                              122012251230                                                                  LeuProGluHisLeuProProGlnSerLeuProAspSerAsnProPhe                              123512401245                                                                  AlaSerAspThrGluAlaProProSerProLeuProLysLeuValVal                              125012551260                                                                  SerProArgHisGluThrGlyAsnArgSerProPheHisGlyArgMet                              1265127012751280                                                              GlnAsnSerProThrHisSerThrAlaSerThrValThrLeuThrGly                              128512901295                                                                  MetSerThrSerGlyGlyGluGluPheCysAlaGlyGlyPheTyrPhe                              130013051310                                                                  AsnSerAlaHisGlnGlyGlnProGlyAlaValProIleSerProHis                              131513201325                                                                  ValAsnValProMetAlaThrAsnMetGluTyrArgAlaValProPro                              133013351340                                                                  ProLeuProProArgArgLysGluArgThrGluSerCysAlaAspMet                              1345135013551360                                                              AlaGlnLysArgGlnAlaProAspAlaProThrLeuProProArgAsp                              136513701375                                                                  GlyGluLeuSerProProProIleProProArgLeuAsnHisSerThr                              138013851390                                                                  GlyIleSerTyrLeuArgGlnSerHisGlyLysSerLysGluPheVal                              139514001405                                                                  GlyAsnSerSerLeuLeuLeuProAsnThrSerSerIleMetIleArg                              141014151420                                                                  ArgAsnSerAlaIleGluLysArgAlaAlaAlaThrSerGlnProAsn                              1425143014351440                                                              GlnAlaAlaAlaGlyProIleSerThrThrLeuValThrValSerGln                              144514501455                                                                  AlaValAlaThrAspGluProLeuAlaAlaThrAspLeuAlaSerGly                              146014651470                                                                  LysLeuLeuAspAspHisIleThrAlaAspThrArgHisValAlaHis                              147514801585                                                                  ValSerGlnHisSerGlnProSerGlyGlyGluHisValGluGlnLeu                              149014951500                                                                  CysProProThrAlaAsnAlaAlaAlaAlaAlaAlaAlaAspAlaSer                              1505151015151520                                                              SerAspLeuLeuAlaAlaProSerThrSerCysHisProSerAlaAla                              152515301535                                                                  ProSerAlaProAlaProPheGluSerAspAlaValAlaLeuValPro                              154015451550                                                                  GlnGlyValLeuSerAspCysHisGluProArgGlyHisThrGlnThr                              155515601565                                                                  SerThrLysThr                                                                  1570                                                                          (2) INFORMATION FOR SEQ ID NO:6:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 1336 amino acids                                                  (B) TYPE: amino acids                                                         (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: protein                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:                                       MetLeuValSerHisLeuIleLeuProLysLysGlnHisProAlaGly                              151015                                                                        ThrMetGlnAlaGlnGlnLeuProTyrGluPhePheSerGluGluAsn                              202530                                                                        AlaProLysTrpArgGlyLeuLeuValProAlaLeuLysLysValGln                              354045                                                                        GlyGlnValHisProThrLeuGluSerAsnAspAspAlaLeuGlnTyr                              505560                                                                        ValGluGluLeuIleLeuGlnLeuLeuAsnMetLeuCysGlnAlaGln                              65707580                                                                      ProArgSerAlaSerAspValGluGluArgValGlnLysSerPhePro                              859095                                                                        HisProIleAspLysTrpAlaIleAlaAspAlaGlnSerAlaIleGlu                              100105110                                                                     LysArgLysArgArgAsnProLeuSerLeuProAlaGluArgIleHis                              115120125                                                                     HisLeuLeuArgGluValLeuGlyTyrLysIleAspHisGlnValSer                              130135140                                                                     ValTyrIleValAlaValLeuGluTyrIleSerAlaAspIleLeuLys                              145150155160                                                                  LeuValGlyAsnTyrValArgAsnIleArgHisTyrGluIleThrLys                              165170175                                                                     GlnAspIleLysValAlaMetCysAlaAspLysValLeuMetAspMet                              180185190                                                                     PheHisGlnAspValGluAspIleAsnIleLeuSerLeuThrAspGlu                              195200205                                                                     GluProSerThrSerGlyGluGlnThrTyrTyrAspLeuValLysAla                              210215220                                                                     PheMetAlaGluIleArgGlnTyrIleArgGluLeuAsnLeuIleIle                              225230235240                                                                  LysValPheArgGluProPheValSerAsnSerLysLeuPheSerSer                              245250255                                                                     AsnAspValGluAsnIlePheSerArgIleValAspIleHisGluLeu                              260265270                                                                     SerValLysLeuLeuGlyHisIleGluAspThrValGluMetThrAsp                              275280285                                                                     GluGlySerProHisProLeuValGlySerCysPheGluAspLeuAla                              290295300                                                                     GluGluLeuAlaPheAspProTyrGluSerTyrAlaArgAspIleLeu                              305310315320                                                                  ArgProGlyPheHisGlyHisPheLeuSerGlnLeuSerLysProGly                              325330335                                                                     AlaAlaLeuTyrLeuGlnSerIleGlyGluGlyPheLysGluAlaVal                              340345350                                                                     GlnTyrValLeuProArgLeuLeuLeuAlaProValTyrHisCysLeu                              355360365                                                                     HisTyrPheGluLeuLeuLysGlnLeuGluGluLysSerGluAspGln                              370375380                                                                     GluAspLysGluCysMetLysGlnAlaIleThrAlaLeuLeuAsnVal                              385390395400                                                                  GlnSerGlyMetGluLysIleCysSerLysSerLeuAlaLysArgArg                              405410415                                                                     LeuSerGluSerAlaCysArgPheTyrSerGlnGlnMetLysGlyLys                              420425430                                                                     GlnLeuAlaIleLysLysMetAsnGluIleGlnLysAsnIleAspGly                              435440445                                                                     TrpGluGlyLysAspIleGlyGlnCysCysAsnGluPheIleMetGlu                              450455460                                                                     GlyThrLeuThrArgValGlyAlaLysHisGluArgHisIlePheLeu                              465470475480                                                                  PheAspGlyLeuMetIleCysCysLysSerAsnHisGlyGlnProArg                              485490495                                                                     LeuProGlyAlaSerSerAlaGluTyrArgLeuLysGluLysPhePhe                              500505510                                                                     MetArgLysValGlnIleAsnAspLysAspAspThrSerGluTyrLys                              515520525                                                                     HisAlaPheGluIleIleLeuLysAspGlyAsnSerValIlePheSer                              530535540                                                                     AlaLysSerAlaGluGluLysAsnAsnTrpMetAlaAlaLeuIleSer                              545550555560                                                                  LeuGlnTyrArgSerThrLeuGluArgMetLeuAspValThrValLeu                              565570575                                                                     GlnGluGluLysGluGluGlnMetArgLeuProSerAlaGluValTyr                              580585590                                                                     ArgPheAlaGluProAspSerGluGluAsnIleLeuPheGluGluAsn                              595600605                                                                     ValGlnProLysAlaGlyIleProIleIleLysAlaGlyThrValLeu                              610615620                                                                     LysLeuIleGluArgLeuThrTyrHisMetTyrAlaAspProAsnPhe                              625630635640                                                                  ValArgThrPheLeuThrThrTyrArgSerPheCysArgProGlnGlu                              645650655                                                                     LeuLeuSerLeuLeuIleGluArgPheGluIleProGluProGluPro                              660665670                                                                     ThrGluAlaAspArgIleAlaIleGluAsnGlyAspGlnProLeuSer                              675680685                                                                     AlaGluLeuLysArgPheArgLysGluTyrIleGlnProValGlnLeu                              690695700                                                                     ArgValLeuAsnValCysArgHisTrpValGluHisHisPheTyrAsp                              705710715720                                                                  PheGluArgAspAlaAspLeuLeuGlnArgMetGluGluPheIleGly                              725730735                                                                     ThrValArgGlyLysAlaMetLysLysTrpValGluSerIleThrLys                              740745750                                                                     IleIleGlnArgLysLysIleAlaArgAspAsnGlyProGlyHisAsn                              755760765                                                                     IleThrPheGlnSerSerProProThrValGluTrpHisIleSerArg                              770775780                                                                     ProGlyHisIleGluThrPheAspLeuLeuThrLeuHisProIleGlu                              785790795800                                                                  IleAlaArgGlnLeuThrLeuLeuGluSerAspLeuTyrArgAlaVal                              805810815                                                                     GlnProSerGluLeuValGlySerValTrpThrLysGluAspLysGlu                              820825830                                                                     IleAsnSerProAsnLeuLeuLysMetIleArgHisThrThrAsnLeu                              835840845                                                                     ThrLeuTrpPheGluLysCysIleValGluThrGluAsnLeuGluGlu                              850855860                                                                     ArgValAlaValValSerArgIleIleGluIleLeuGlnValPheGln                              865870875880                                                                  GluLeuAsnAsnPheAsnGlyValLeuGluValValSerAlaMetAsn                              885890895                                                                     SerSerProValTyrArgLeuAspHisThrPheGluGlnIleProSer                              900905910                                                                     ArgGlnLysLysIleLeuGluGluAlaHisGluLeuSerGluAspHis                              915920925                                                                     TyrLysLysTyrLeuAlaLysLeuArgSerIleAsnProProCysVal                              930935940                                                                     ProPhePheGlyIleTyrLeuThrAsnIleLeuLysThrGluGluGly                              945950955960                                                                  AsnProGluValLeuArgArgHisGlyLysGluLeuIleAsnPheSer                              965970975                                                                     LysArgArgArgValAlaGluIleThrGlyGluIleGlnGlnTyrGln                              980985990                                                                     AsnGlnProTyrCysLeuArgValGluProAspIleLysArgPhePhe                              99510001005                                                                   GluAsnLeuAsnProMetGlyAsnSerMetGluLysGluPheThrAsp                              101010151020                                                                  TyrLeuPheAsnLysSerLeuGluIleGluProArgHisProLysPro                              1025103010351040                                                              LeuProArgPheProLysLysTyrSerTyrProLeuLysSerProGly                              104510501055                                                                  ValArgProSerAsnProArgProGlyThrMetArgHisProThrPro                              106010651070                                                                  LeuGlnGlnGluProArgLysIleSerTyrSerArgIleProGluSer                              107510801085                                                                  GluThrGluSerThrAlaSerAlaProAsnSerProArgThrProLeu                              109010951100                                                                  ThrProProProAlaSerGlyThrSerSerAsnThrAspValCysSer                              1105111011151120                                                              ValPheAspSerAspHisSerAlaSerProPheHisSerArgSerAla                              112511301135                                                                  SerValSerSerIleSerLeuSerLysGlyThrAspGluValProVal                              114011451150                                                                  ProProProValProProArgArgArgProGluSerAlaProAlaGlu                              115511601165                                                                  SerSerProSerLysIleMetSerLysHisLeuAspSerProProAla                              117011751180                                                                  IleProProArgGlnProThrSerLysAlaTyrSerProArgTyrSer                              1185119011951200                                                              IleSerAspArgThrSerIleSerAspProProGluSerProProLeu                              120512101215                                                                  LeuProProArgGluProValArgThrProAspValPheSerSerSer                              122012251230                                                                  ProLeuHisLeuGlnProProProLeuGlyLysLysSerAspHisGly                              123512401245                                                                  AsnAlaPhePheProAsnSerProSerProPheThrProProProPro                              125012551260                                                                  GlnThrProSerProHisGlyThrArgArgHisLeuProSerProPro                              1265127012751280                                                              LeuThrGlnGluMetAspLeuHisSerIleAlaGlyProProValPro                              128512901295                                                                  ProArgGlnSerThrSerGlnLeuIleProLysLeuProProLysThr                              130013051310                                                                  TyrLysArgGluHisThrHisProSerMetHisArgAspGlyProPro                              131513201325                                                                  LeuLeuGluAsnAlaHisSerSer                                                      13301335                                                                      (2) INFORMATION FOR SEQ ID NO:7:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 108 base pairs                                                    (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: DNA                                                       (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:                                       TGTGTTCTAGTTGGGTGCAAGGTCTAGCCTAAGGCAATGCTTGTCTCC48                            CysValLeuValGlyCysLysValProLysAlaMetLeuValSer                                 151015                                                                        CACCTCATCCTGCCAAGGAAGCAGCACCCCGCGGGCACCATGCAGGCG96                            HisLeuIleLeuProArgLysGlnHisProAlaGlyThrMetGlnAla                              202530                                                                        CAGCAGCTGCCT108                                                               GlnGlnLeuPro                                                                  35                                                                            (2) INFORMATION FOR SEQ ID NO:8:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 57 base pairs                                                     (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: DNA                                                       (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:                                       GCCCCTCCGCCCGCCCCGAGGCGCCCCGCGGGCACCATGCAGGCGCAG48                            AlaProProProAlaProArgArgProAlaGlyThrMetGlnAlaGln                              151015                                                                        CAGCTGCCT57                                                                   GlnLeuPro                                                                     (2) INFORMATION FOR SEQ ID NO:9:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 430 amino acids                                                   (B) TYPE: amino acids                                                         (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: protein                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:                                       IleLysGlyAlaThrLeuCysLysLeuIleGluArgLeuThrTyrHis                              151015                                                                        IleTyrAlaAspProThrPheValArgThrPheLeuThrThrTyrArg                              202530                                                                        TyrPheCysSerProGlnGlnLeuLeuGlnLeuLeuValGluArgPhe                              354045                                                                        AsnIleProAspProSerLeuValTyrGlnAspThrGlyThrAlaGly                              505560                                                                        AlaGlyGlyMetGlyGlyValGlyGlyAspLysGluHisLysAsnSer                              65707580                                                                      HisArgGluAspTrpLysArgTyrArgLysGluTyrValGlnProVal                              859095                                                                        GlnPheArgValLeuAsnValLeuArgHisTrpValAspHisHisPhe                              100105110                                                                     TyrAspPheGluLysAspProMetLeuLeuGluLysLeuLeuAsnPhe                              115120125                                                                     LeuGluHisValAsnGlyLysSerMetArgLysTrpValAspSerVal                              130135140                                                                     LeuLysIleValGlnArgLysAsnGluGlnGluLysSerAsnLysLys                              145150155160                                                                  IleValTyrAlaTyrGlyHisAspProProProIleGluHisHisLeu                              165170175                                                                     SerValProAsnAspGluIleThrLeuLeuThrLeuHisProLeuGlu                              180185190                                                                     LeuAlaArgGlnLeuThrLeuLeuGluPheGluMetTyrLysAsnVal                              195200205                                                                     LysProSerGluLeuValGlySerProTrpThrLysLysAspLysGlu                              210215220                                                                     ValLysSerProAsnLeuLeuLysIleMetLysHisThrThrAsnVal                              225230235240                                                                  ThrArgTrpIleGluLysSerIleThrGluAlaGluAsnTyrGluGlu                              245250255                                                                     ArgLeuAlaIleMetGlnArgAlaIleGluValMetMetValMetLeu                              260265270                                                                     GluLeuAsnAsnPheAsnGlyIleLeuSerIleValAlaAlaMetGly                              275280285                                                                     ThrAlaSerValTyrArgLeuArgTrpThrPheGlnGlyLeuProGlu                              290295300                                                                     ArgTyrArgLysPheLeuGluGluCysArgGluLeuSerAspAspHis                              305310315320                                                                  LeuLysLysTyrGlnGluArgLeuArgSerIleAsnProProCysVal                              325330335                                                                     ProPhePheGlyArgTyrLeuThrAsnIleLeuHisLeuGluGluGly                              340345350                                                                     AsnProAspLeuLeuAlaAsnThrGluLeuIleAsnPheSerLysArg                              355360365                                                                     ArgLysValAlaGluIleIleGlyGluIleGlnGlnTyrGlnAsnGln                              370375380                                                                     ProTyrCysLeuAsnGluGluSerThrIleArgGlnPhePheGluGln                              385390395400                                                                  LeuAspProPheAsnGlyLeuSerAspLysGlnMetSerAspTyrLeu                              405410415                                                                     TyrAsnGluSerLeuArgIleGluProArgGlyCysLysThr                                    420425430                                                                     (2) INFORMATION FOR SEQ ID NO:10:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 423 amino acids                                                   (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: protein                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:                                      IleLysAlaGlyThrValLeuLysLeuIleGluArgLeuThrTyr                                 151015                                                                        HisMetTyrAlaAspProAsnPheValArgThrPheLeuThrThr                                 202530                                                                        TyrArgSerPheCysArgProGlnGluLeuLeuSerLeuLeuIle                                 354045                                                                        GluArgPheGluIleProGluProGluProThrGluAlaAspArg                                 505560                                                                        IleAlaIleGluAsnGlyAspGlnProLeuSerAlaGluLeuLys                                 657075                                                                        ArgPheArgLysGluTyrIleGlnProValGlnLeuArgValLeu                                 808590                                                                        AsnValCysArgHisTrpValGluHisHisPheTyrAspPheGlu                                 95100105                                                                      ArgAspAlaAspLeuLeuGlnArgMetGluGluPheIleGlyThr                                 110115120                                                                     ValArgGlyLysAlaMetLysLysTrpValGluSerIleThrLys                                 125130135                                                                     IleIleGlnArgLysLysIleAlaArgAspAsnGlyProGlyHis                                 140145150                                                                     AsnIleThrPheGlnSerSerProProThrValGluTrpHisIle                                 155160165                                                                     SerArgProGlyHisIleGluThrPheAspLeuLeuThrLeuHis                                 170175180                                                                     ProIleGluIleAlaArgGlnLeuThrLeuLeuGluSerAspLeu                                 185190195                                                                     TyrArgAlaValGlnProSerGluLeuValGlySerValTrpThr                                 200205210                                                                     LysGluAspLysGluIleAsnSerProAsnLeuLeuLysMetIle                                 215220225                                                                     ArgHisThrThrAsnLeuThrLeuTrpPheGluLysCysIleVal                                 230235240                                                                     GluThrGluAsnLeuGluGluArgValAlaValValSerArgIle                                 245250255                                                                     IleGluIleLeuGlnValPheGlnGluLeuAsnAsnPheAsnGly                                 260265270                                                                     ValLeuGluValValSerAlaMetAsnSerSerProValTyrArg                                 275280285                                                                     LeuAspHisThrPheGluGlnIleProSerArgGlnLysLysIle                                 290295300                                                                     LeuGluGluAlaHisGluLeuSerGluAspHisTyrLysLysTyr                                 305310315                                                                     LeuAlaLysLeuArgSerIleAsnProProCysValProPhePhe                                 320325330                                                                     GlyIleTyrLeuThrAsnIleLeuLysThrGluGluGlyAsnPro                                 335340345                                                                     GluValLeuArgArgHisGlyLysGluLeuIleAsnPheSerLys                                 350355360                                                                     ArgArgArgValAlaGluIleThrGlyGluIleGlnGlnTyrGln                                 365370375                                                                     AsnGlnProTyrCysLeuArgValGluProAspIleLysArgPhe                                 380385390                                                                     PheGluAsnLeuAsnProMetGlyAsnSerMetGluLysGluPhe                                 395400405                                                                     ThrAspTyrLeuPheAsnLysSerLeuGluIleGluProArgHis                                 410415420                                                                     ProLysPro                                                                     (2) INFORMATION FOR SEQ ID NO:11:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 423 amino acids                                                   (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: protein                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:                                      IleLysGlyGlyThrValValLysLeuIleGluArgLeuThrTyr                                 151015                                                                        HisMetTyrAlaAspProAsnPheValArgThrPheLeuThrThr                                 202530                                                                        TyrArgSerPheCysLysProGlnGluLeuLeuAsnLeuLeuIle                                 354045                                                                        GluArgPheGluIleProGluProGluProThrGluAlaAspLys                                 505560                                                                        LeuAlaLeuGluLysGlyGluGlnProIleSerAlaAspLeuLys                                 657075                                                                        ArgPheArgLysGluTyrValGlnProValGlnLeuArgValLeu                                 808590                                                                        AsnValPheArgHisTrpValGluHisHisTyrTyrAspPheGlu                                 95100105                                                                      ArgAspLeuGluLeuLeuGluArgLeuGluSerPheIleSerSer                                 110115120                                                                     ValArgGlyLysAlaMetLysLysTrpValGluSerIleAlaLys                                 125130135                                                                     IleIleLysArgLysLysGlnAlaGlnAlaAsnGlyIleSerHis                                 140145150                                                                     AsnIleThrPheGluSerSerProProProValGluTrpHisIle                                 155160165                                                                     SerArgThrGlyGlnPheGluThrPheAspLeuMetThrLeuHis                                 170175180                                                                     ProIleGluIleAlaArgGlnLeuThrLeuLeuGluSerAspLeu                                 185190195                                                                     TyrArgLysValGlnProSerGluLeuValGlySerValTrpThr                                 200205210                                                                     LysGluAspLysGluIleAsnSerProAsnLeuLeuLysMetIle                                 215220225                                                                     ArgHisThrThrAsnLeuThrLeuTrpPheGluLysCysIleVal                                 230235240                                                                     GluAlaGluAsnPheGluGluArgValAlaValLeuSerArgIle                                 245250255                                                                     ValGluIleLeuGlnValPheGlnAspLeuAsnAsnPheAsnGly                                 260265270                                                                     ValLeuGluIleValSerAlaValAsnSerValSerValTyrArg                                 275280285                                                                     LeuAspHisThrPheGluAlaLeuGlnGluArgLysArgArgIle                                 290295300                                                                     LeuAspAspAlaValGluLeuSerGlnAspHisPheLysLysTyr                                 305310315                                                                     LeuValLysLeuLysSerIleAsnProProCysValProPhePhe                                 320325330                                                                     GlyIleTyrLeuThrAsnIleLeuLysThrGluGluGlyAsnSer                                 335340345                                                                     AspPheLeuLysArgLysGlyLysAspLeuIleAsnPheSerLys                                 350355360                                                                     ArgArgLysValAlaGluIleThrGlyGluIleGlnGlnTyrGln                                 365370375                                                                     AsnGlnProTyrCysLeuArgThrGluProGluMetArgArgPhe                                 380385390                                                                     PheGluAsnLeuAsnProMetGlyIleLeuSerGluLysGluPhe                                 395400405                                                                     ThrAspTyrLeuPheAsnLysSerLeuGluIleGluProArgAsn                                 410415420                                                                     CysLysGln                                                                     (2) INFORMATION FOR SEQ ID NO:12:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 426 amino acids                                                   (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: protein                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:                                      IleArgGlyGlyThrLysGluAlaLeuIleGluHisLeuThrSer                                 151015                                                                        HisGluLeuValAspAlaAlaPheAsnValThrMetLeuIleThr                                 202530                                                                        PheArgSerIleLeuThrThrArgGluPhePheTyrAlaLeuIle                                 354045                                                                        TyrArgTyrAsnLeuTyrProProGluGlyLeuSerTyrAspAsp                                 505560                                                                        TyrAsnIleTrpIleGluLysLysSerAsnProIleLysCysArg                                 657075                                                                        ValValAsnIleMetArgThrPheLeuThrGlnTyrTrpThrArg                                 808590                                                                        AsnTyrTyrGluProGlyIleProLeuIleLeuAsnPheAlaLys                                 95100105                                                                      MetValValSerGluLysIleProGlyAlaGluAspLeuLeuGln                                 110115120                                                                     LysIleAsnGluLysLeuIleAsnGluAsnGluLysGluProVal                                 125130135                                                                     AspProLysGlnGlnAspSerValSerAlaValValGlnThrThr                                 140145150                                                                     LysArgAspAsnLysSerProIleHisMetSerSerSerSerLeu                                 155160165                                                                     ProSerSerAlaSerSerAlaPhePheArgLeuLysLysLeuLys                                 170175180                                                                     LeuLeuAspIleAspProTyrThrTyrAlaThrGlnLeuThrVal                                 185190195                                                                     LeuGluHisAspLeuTyrLeuArgIleThrMetPheGluCysLeu                                 200205210                                                                     AspArgAlaTrpGlyThrLysTyrCysAsnMetGlyGlySerPro                                 215220225                                                                     AsnIleThrLysPheIleAlaAsnAlaAsnThrLeuThrAsnPhe                                 230235240                                                                     ValSerHisThrIleValLysGlnAlaAspValLysThrArgSer                                 245250255                                                                     LysLeuThrGlnTyrPheValThrValAlaGlnHisCysLysGlu                                 260265270                                                                     LeuAsnAsnPheSerSerMetThrAlaIleValSerAlaLeuTyr                                 275280285                                                                     SerSerProIleTyrArgLeuLysLysThrTrpAspLeuValSer                                 290295300                                                                     ThrGluSerLysAspLeuLeuLysAsnLeuAsnAsnLeuMetAsp                                 305310315                                                                     SerLysArgAsnPheValLysTyrArgGluLeuLeuArgSerVal                                 320325330                                                                     ThrAspValAlaCysValProPhePheGlyValTyrLeuSerAsp                                 335340345                                                                     LeuThrPheThrPheValGlyAsnProAspPheLeuHisAsnSer                                 350355360                                                                     ThrAsnIleIleAsnPheSerLysArgThrLysIleAlaAsnIle                                 365370375                                                                     ValGluGluIleIleSerPheLysArgPheHisTyrLysLeuLys                                 380385390                                                                     ArgLeuAspAspIleGlnThrValIleGluAlaSerLeuGluAsn                                 395400405                                                                     ValProHisIleGluLysGlnTyrGlnLeuSerLeuGlnValGlu                                 410415420                                                                     ProProSerGlyAsnThr                                                            425                                                                           (2) INFORMATION FOR SEQ ID NO:13:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 418 amino acids                                                   (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: protein                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:                                      IleLysGlyGlySerLysHisAlaLeuIleSerTyrLeuThrAsp                                 151015                                                                        AsnGluLysLysAspLeuPhePheAsnIleThrPheLeuIleThr                                 202530                                                                        PheArgSerIlePheThrThrThrGluPheLeuSerTyrLeuIle                                 354045                                                                        SerGlnTyrAsnLeuAspProProGluAspLeuCysPheGluGlu                                 505560                                                                        TyrAsnGluTrpValThrLysLysLeuIleProValLysCysArg                                 657075                                                                        ValValGluIleMetThrThrPhePheLysGlnTyrTrpPhePro                                 808590                                                                        GlyTyrAspGluProAspLeuAlaThrLeuAsnLeuAspTyrPhe                                 95100105                                                                      AlaGlnValAlaIleLysGluAsnIleThrGlySerValGluLeu                                 110115120                                                                     LeuLysGluValAsnGlnLysPheLysLeuGlyAsnIleGlnGlu                                 125130135                                                                     AlaThrAlaProMetLysThrLeuAspGlnGlnIleCysGlnAsp                                 140145150                                                                     HisTyrSerGlyThrLeuTyrSerThrThrGluSerIleLeuAla                                 155160165                                                                     ValAspProValLeuPheAlaThrGlnLeuThrIleLeuGluHis                                 170175180                                                                     GluIleTyrCysGluIleThrThrPheAspCysLeuGlnLysIle                                 185190195                                                                     TrpLysAsnLysTyrThrLysSerTyrGlyAlaSerProGlyLeu                                 200205210                                                                     AsnGluPheIleSerPheAlaAsnLysLeuThrAsnPheIleSer                                 215220225                                                                     TyrSerValValLysGluAlaAspLysSerLysArgAlaLysLeu                                 230235240                                                                     LeuSerHisPheIlePheIleAlaGluTyrCysArgLysPheAsn                                 245250255                                                                     AsnPheSerSerMetThrAspIleIleSerAlaLeuTyrSerSer                                 260265270                                                                     ProIleTyrArgLeuGluLysThrTrpGlnAlaValIleProGln                                 275280285                                                                     ThrArgAspLeuLeuGlnSerLeuAsnLysLeuMetAspProLys                                 290295300                                                                     LysAsnPheIleAsnTyrArgAsnGluLeuLysSerLeuHisSer                                 305310315                                                                     AlaProCysValProPhePheGlyValTyrLeuSerAspLeuThr                                 320325330                                                                     PheThrAspSerGlyAsnProAspTyrLeuValLeuGluHisGly                                 335340345                                                                     LeuLysGlyValHisAspGluLysLysTyrIleAsnPheAsnLys                                 350355360                                                                     ArgSerArgLeuValAspIleLeuGlnGluIleIleTyrPheLys                                 365370375                                                                     LysThrHisTyrAspPheThrLysAspArgThrValIleGluCys                                 380385390                                                                     IleSerAsnSerLeuGluAsnIleProHisIleGluLysGlnTyr                                 395400405                                                                     GlnLeuSerLeuIleIleGluProLysProArgLysLys                                       410415                                                                        (2) INFORMATION FOR SEQ ID NO:14:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 402 amino acids                                                   (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: protein                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14:                                      IleLysThrAlaThrLeuValPheIleIleAsnTyrLeuLeuArg                                 151015                                                                        ThrAspIleAspSerThrPhePheThrThrIlePheLeuAsnThr                                 202530                                                                        TyrAlaSerMetIleSerSerSerAspLeuPheSerIleLeuGly                                 354045                                                                        AlaHisPheArgPheIleCysSerLeuAsnPheGlyLysIleSer                                 505560                                                                        PheIleSerHisGluPheTyrArgValSerLysArgPheLeuAsp                                 657075                                                                        IleLeuLeuIleTrpPheGluSerTyrLeuValGluGluLeuAsp                                 808590                                                                        AsnSerLysSerIlePhePheLeuPheLysIleTyrLysValPhe                                 95100105                                                                      GluValPheValValProHisPheAlaSerAlaGluGluLeuLeu                                 110115120                                                                     HisSerLeuSerHisLeuLeuHisHisProSerThrLysArgSer                                 125130135                                                                     HisLysMetLeuGluGlyLysGluLeuSerGlnGluLeuGluAsp                                 140145150                                                                     LeuSerLeuHisAsnSerProAspProIleIleTyrLysAspGlu                                 155160165                                                                     LeuValLeuLeuLeuProProArgGluIleAlaLysGlnLeuCys                                 170175180                                                                     IleLeuGluPheGlnSerPheSerHisIleSerArgIleGlnPhe                                 185190195                                                                     LeuThrLysIleTrpAspGluLeuAsnArgPheSerProLysGlu                                 200205210                                                                     LysThrSerThrPheTyrLeuSerAsnHisLeuValAsnPheVal                                 215220225                                                                     ThrGluThrIleValGlnGluGluGluProArgArgArgThrAsn                                 230235240                                                                     ValLeuAlaTyrPheIleGlnValCysAspTyrLeuArgGluLeu                                 245250255                                                                     AsnAsnPheAlaSerLeuPheSerIleIleSerAlaLeuAsnSer                                 260265270                                                                     SerProIleHisArgLeuArgLysThrTrpAlaAsnLeuAsnSer                                 275280285                                                                     LysThrLeuAlaSerPheGluLeuLeuAsnAsnLeuThrGluAla                                 290295300                                                                     ArgLysAsnPheSerAsnTyrArgAspCysLeuGluAsnCysVal                                 305310315                                                                     LeuProCysValProPheLeuGlyValTyrPheThrAspLeuThr                                 320325330                                                                     PheLeuLysThrGlyAsnLysAspAsnPheGlnAsnMetIleAsn                                 335340345                                                                     PheAspLysArgThrLysValThrArgIleLeuAsnGluIleLys                                 350355360                                                                     LysPheGlnSerValGlyTyrMetPheAsnProIleAsnGluVal                                 365370375                                                                     GlnGluLeuLeuAsnGluValIleSerArgGluArgAsnThrAsn                                 380385390                                                                     AsnIleTyrGlnArgSerLeuThrValGluProArg                                          395400                                                                        (2) INFORMATION FOR SEQ ID NO:15:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 362 amino acids                                                   (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: protein                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:                                      ProSerProPheAspSerAlaAsnLeuLeuLeuAsnPheArgAsp                                 151015                                                                        TrpThrThrAspAsnAlaLeuLeuGlnGluLeuLeuLeuSerTyr                                 202530                                                                        ProThrIleAsnLysAsnLysHisLysAsnHisSerValProArg                                 354045                                                                        LeuIleGlnIleTrpValGluSerTyrTrpGlnAspSerGluThr                                 505560                                                                        ThrLeuLysAspIleLeuAsnPheTrpTyrSerHisLeuAlaGlu                                 657075                                                                        TyrTyrGluTyrGlnGluLeuPheAlaAspIleValGlnLeuPhe                                 808590                                                                        IleAsnLysLysArgThrArgGlnLeuLysIleHisTyrIleGly                                 95100105                                                                      LeuThrAspLysGluIleGluGluAsnLysProProLeuAspTyr                                 110115120                                                                     GluAsnLeuPheLeuGlnTyrGluIleAspLysThrAsnAlaAsn                                 125130135                                                                     AspGluLeuCysGlyAlaThrAspLeuSerAspLeuLeuPheGln                                 140145150                                                                     TrpLysGlnGlyGluProLeuGluValGluAlaPheAlaLeuAsn                                 155160165                                                                     ValSerProTrpSerLeuAlaLysThrLeuThrLeuLeuGluSer                                 170175180                                                                     SerLeuTyrLeuAspIleGluThrIleGluPheThrArgHisPhe                                 185190195                                                                     LysHisAsnAspThrThrIleAspSerValPheThrLeuSerAsn                                 200205210                                                                     GlnLeuSerSerTyrValLeuGluThrThrLeuGlnGlnThrHis                                 215220225                                                                     ThrIleSerTyrTrpLeuGlnValAlaLeuAlaCysLeuTyrLeu                                 230235240                                                                     ArgAsnLeuAsnSerLeuAlaSerIleIleThrSerLeuGlnAsn                                 245250255                                                                     HisSerIleGluArgLeuSerLeuProIleAspValLysSerAsp                                 260265270                                                                     HisLeuPheGlnArgLeuLysValValValHisProAsnAsnAsn                                 275280285                                                                     TyrAsnValTyrArgArgThrIleLysHisIlePheHisSerGln                                 290295300                                                                     LeuProCysValProPheThrSerLeuLeuIleArgAspIleThr                                 305310315                                                                     PheIleArgAspGlyAsnAspThrPheThrLysAspGlyAsnAsn                                 320325330                                                                     ValAsnMetGlnLysPheAsnGlnIleThrLysIleValAlaPhe                                 335340345                                                                     AlaGlnTyrLeuGlnGlnLysGlnTyrGluAspIleHisCysSer                                 350355360                                                                     AsnThr                                                                        __________________________________________________________________________

I claim:
 1. An isolated DNA molecule comprising a nucleotide sequence encoding murine son of sevenless gene 1 (mSOS1) polypeptide having the amino acid sequence of SEQ ID NO:2, or a fragment of at least 20 nucleotides of said DNA molecule.
 2. The isolated DNA molecule of claim 1, wherein said nucleotide sequence encoding mSOS1 has the nucleotide sequence shown in SEQ ID NO:1.
 3. An isolated DNA molecule comprising a nucleotide sequence encoding murine son of sevenless gene 2 (mSOS2) polypeptide having the amino acid sequence of SEQ ID NO:4, or a fragment of at least 20 nucleotides of said DNA molecule.
 4. The isolated DNA molecule of claim 3, wherein said nucleotide sequence encoding mSOS2 has the nucleotide sequence shown in SEQ ID NO:3.
 5. A vector comprising the isolated DNA molecule of any of claims 1, 3, 2 or
 4. 6. An isolated mSOS1 polypeptide having the amino acid sequence shown in SEQ ID NO:2, or a fragment of at least 20 amino acids thereof.
 7. An isolated mSOS2 polypeptide having the amino acid sequence shown in SEQ ID NO:4, or a fragment of at least 20 amino acids thereof.
 8. A method for detecting a mutant mSOS1 gene comprising the steps of:(A) obtaining DNA encoding mSOS1 protein from a test subject; (B) determining:(i) the nucleotide sequence, and optionally the encoded amino acid sequence, of the resulting DNA obtained in step (A), or (ii) the chromosomal location of the resulting DNA obtained in step (A), or (iii) the structure of the resulting DNA obtained in step (A); (C) comparing the resulting nucleotide sequence or chromosomal location or structure obtained in step (B) with the nucleotide sequence, chromosomal location or structure of wild-type mSOS1 gene, wherein the nucleotide sequence of wild-type mSOS1 gene is that shown in SEQ ID NO:1, or comparing the resulting encoded amino acid sequence with the amino acid sequence of wild-type mSOS1 protein, wherein the amino acid sequence of wild-type mSOS1 protein is that shown in SEQ ID NO:2,wherein a mutant mSOS1 gene is detected when the resulting nucleotide sequence, chromosomal location or structure obtained in step (B) differs from that of SEQ ID NO:1, or when the resulting encoded amino acid sequence obtained in step (B) differs from that of SEQ ID NO:2.
 9. The method according to claim 8, wherein the structure in step (B) is determined by carrying out restriction fragment polymorphism analysis or analysis of amplified products.
 10. A method for detecting a mutant mSOS2 gene comprising the steps of:(A) obtaining DNA encoding mSOS2 protein from a test subject; (B) determining:(i) the nucleotide sequence, and optionally the encoded amino acid sequence, of the resulting DNA obtained in step (A), or (ii) the chromosomal location of the resulting DNA obtained in step (A), or (iii) the structure of the resulting DNA obtained in step (A); (C) comparing the resulting nucleotide sequence or chromosomal location or structure obtained in step (B) with the nucleotide sequence, chromosomal location or structure of wild-type mSOS1 gene, wherein the nucleotide sequence of wild-type mSOS2 gene is that shown in SEQ ID NO:3, or comparing the resulting encoded amino acid sequence with the amino acid sequence of wild-type mSOS2 protein, wherein the amino acid sequence of wild-type mSOS1 protein is that shown in SEQ ID NO:4,wherein a mutant mSOS2 gene is detected when the resulting nucleotide sequence, chromosomal location or structure obtained in step (B) differs from that of SEQ ID NO:3, or when the resulting encoded amino acid sequence obtained in step (B) differs from that of SEQ ID NO:4.
 11. The method according to claim 10, wherein the structure in step (B) is determined by carrying out restriction fragment polymorphism analysis or analysis of amplified products.
 12. A method for detecting a mutant mSOS1 protein comprising the steps of:(A) obtaining mSOS1 protein from a test subject; (B) determining the amino acid sequence of the resulting mSOS1 protein obtained in step (A); (c) comparing the resulting amino acid sequence obtained in step (B) with the amino acid sequence of wild-type mSOS1 protein, wherein the amino acid sequence of wild-type mSOS1 protein is that shown in SEQ ID NO:2,wherein a mutant mSOS1 protein is detected when the resulting amino acid sequence obtained in step (B) differs from that of SEQ ID NO:
 2. 13. A method for detecting a mutant mSOS2 protein comprising the steps of:(A) obtaining mSOS2 protein from a test subject; (B) determining the amino acid sequence of the resulting mSOS2 protein obtained in step (A); (C) comparing the resulting amino acid sequence obtained in step (B) with the amino acid sequence of wild-type mSOS2 protein, wherein the amino acid sequence of wild-type mSOS2 protein is that shown in SEQ ID NO:4,wherein a mutant mSOS2 protein is detected when the resulting amino acid sequence obtained in step (B) differs from that of SEQ ID NO:4. 